Cancer

The history of cancer as a known disease

The genetics of cancer

Types of cancers

Causes and symptoms

Diagnosis

Treatment

Prognosis

Prevention

Resources

Cancer is not just one disease, but a large group of almost 100 diseases. Its two main characteristics are uncontrolled growth of the cells in the human body and the ability of these cells to migrate from the original site and spread to distant sites. If the spread is not controlled, cancer can result in death.

Of all premature deaths, one out of every four deaths in the United States is from cancer. It is second only to heart disease as a cause of death in the United States. According to the American Cancer Society (ACS), as of 2006, over 550 million people in the United States die of cancer each year. Annually, about 1.4 million new cases of cancer will be diagnosed, excluding preinvasive cancer (but including urinary bladder cancer) and nonmelanoma skin cancer (in which about one million cases will be diagnosed).

Cancer can attack anyone. Since the occurrence of cancer increases as people age, most of the cases are seen in adults, middle-aged or older. The most common cancers are skin cancer, lung cancer, colon cancer, breast cancer (in women), and prostate cancer (in men). In addition, cancer of the kidneys, ovaries, uterus, pancreas, bladder, rectum, and blood and lymph node cancer (leukemia and lymphomas) are also included among the 12 major cancers that affect most Americans.

The history of cancer as a known disease

The term cancer derives from the observation by Hippocrates in 400 BC that the veins radiating from a breast cancer resembled the legs of a crab, hence karkinoma in Greek and cancer in Latin. Cancer is not a single disease, but is many different diseases that all share common biological and pathological characteristics. In most western societies, cancer is a leading cause of death. The disease may develop in any body tissue or organ and over one hundred different types of cancer can occur in adults. Cancer also occurs in children and may even be present at birth.

The first clues to the cause of cancer came over two hundred years ago from an observation by Percivall Pott, a London doctor, who in 1775 found a high incidence of scrotal cancer in men who had worked as chimney sweeps. Later, radiation was found to cause skin cancer and tragically Marie Curie (1867–1934), the discoverer of x rays, died of a cancer caused by prolonged exposure to radiation. During the second half of the twentieth century, epidemiologists (those who study disease in populations) linked exposure to certain environmental toxins and particular types of cancer. Most notably, cigarette smoking and lung cancer, sunlight and skin cancer, and certain industrial chemicals were linked as the cause of bladder and liver cancer. Finally several viruses were also been implicated in causing cancer, such as the hepatitis B virus and cancer of the liver, the Epstein Barr virus and lymphoma, and the human papilloma virus and cancer of the cervix. These important observations all suggested that specific external environmental agents could cause specific cancers.

How then could a diverse range of external agents such as chemicals, radiation, and viruses, all lead to the development of cancer?. The answer to this question has come over the last 30 years from two different lines of investigation: studies on cancer causing viruses and research into the genetics of some rare cancers in children.

In 1910, Frances Peyton Rous (1879–1970) isolated a virus from a cancer in chickens (a sarcoma) that caused new sarcomas to develop when infected into healthy chickens. Rous’s work languished for over 50 years until he was awarded a Nobel Prize in 1966. By this time, methods for the study of viruses and cancer had improved considerably and many new animal derived viruses were found to cause cancer in a range of species. These viruses could also induce cancer-like changes when introduced into normal cells grown in the laboratory. A genetic study of these cancer causing viruses identified a small number of genes termed viral onco-genes (v-oncogenes) which, when introduced into cells, could transform the normal cells into malignant cells.

The presence of viral oncogenes led to the search for endogenous cellular oncogenes, which might cause cancer. In a crucial experiment in the late 1970s, DNA (deoxyribonucleic acid) from mouse cells that had been transformed by a chemical carcinogen, was transfected into normal mouse cells. The normal mouse cells became malignant suggesting that a gene within the cancer (a proto-oncogene) had been mutated by exposure to the chemical and was able to induce cancer. Surprisingly, when these endogenous cellular oncogenes were eventually isolated they were found to be homologous to virally derived oncogenes.

In the early 1970s, American pediatrician and scientist Alfred Knudson at the Fox Chase Cancer Center studied retinoblastoma, a rare childhood eye cancer that is sometimes inherited but is most often sporadic. He observed that children who had inherited retinoblastoma often had the cancer at birth, and were at high risk of developing multiple cancers in both eyes. Children with later onset retinoblastoma usually had no family history and developed isolated tumors. Knudson reasoned that children with inherited retinoblastoma had a germline mutation in one allele of a recessive cancer gene. The germline mutation was the first of two hits in knocking out a recessive cancer gene. This is known as Knudson’s two hit hypothesis. Later genetic studies found the first hit in children with inherited retinoblastoma to be a partial deletion of the long arm of chromosome 13 causing loss of the tumor suppressor gene, RB1.

These two directions of study independently identified two different classes of cancer gene, the oncogene and tumor suppressor gene, that when mutated in a given cell can set in train the sequence of events leading to the development of a cancer.

The genetics of cancer

Cancer, by definition, is a disease of the genes. Cancer is also the most common genetic disease in humans, but only rarely is it inherited. A gene is a small part of DNA, which is the master molecule of the cell. Genes make proteins, which are the ultimate workhorses of the cells. It is these proteins that allow human bodies to carry out all the many processes that permit people to breathe, think, move, etc.

Throughout people’s lives, the cells in their bodies are growing, dividing, and replacing themselves. Many genes produce proteins that are involved in controlling the processes of cell growth and division. An alteration (mutation) to the DNA molecule can disrupt the genes and produce faulty proteins. This causes the cell to become abnormal and lose its restraints on growth. The abnormal cell begins to divide uncontrollably and eventually forms a new growth known as a tumor or neoplasm (which is the medical term for cancer meaning new growth).

In a healthy individual, the immune system can recognize the neoplastic cells and destroy them before they get a chance to divide. However, some mutant cells may escape immune detection and survive to become tumors or cancers.

Tumors are of two types: benign or malignant. A benign tumor is slow growing, does not spread or invade surrounding tissue, and once it is removed, it does not usually recur. A malignant tumor, on the other hand, invades surrounding tissue and spreads to other parts of the body. The hallmark of a malignant cancer is the uncontrolled clonal proliferation and spread of abnormal cancer cells. If the cancer cells have spread to the surrounding tissues, then, even after the malignant tumor is removed, it generally recurs.

Many cancers are caused by changes in the cell’s DNA because of damage due to the environment. Environmental factors that are responsible for causing the initial mutation in the DNA are called carcinogens. There are many types of carcinogens, such as asbestos and noitrosonornicotine (in cigarettes).

There are some cancers that have a genetic basis. In other words, an individual could inherit faulty DNA from his/her parents, which could predispose that person to getting cancer. While there is scientific evidence that both factors (environmental and genetic) play a role, less than 10% of all cancers are purely hereditary. Cancers that are known to have a hereditary link are breast cancer, colon cancer, ovarian cancer, and uterine cancer. Besides genes, certain physiological traits could be inherited and could contribute to cancers. For example, inheriting fair skin makes a person more likely to develop skin cancer, but only if they also have prolonged exposure to intensive sunlight.

Most cancers are sporadic and arise in a particular tissue such as the colon, breast, lung, or skin when normal cells acquire mutations in one or more onco-genes or tumor suppressor genes. The acquisition of multiple new genetic changes is what sets the cancer cell apart from the normal cells in its surrounding tissues.

The cancer cell develops when a normal cell in an organ or tissue acquires the capacity to divide in an uncontrolled fashion. Over time the developing cancer cell starts to multiply in a clonal fashion, begins to appear different (anaplastic or undifferentiated), and progressively acquires other characteristics, such as the capacity metastasise while losing cell-to-cell adhesion. The continued acquisition of new biologic characteristics is the key to many aggressive cancers evading the host defenses, and to the resisting some treatments such chemotherapy and radiotherapy.

It is important to appreciate that oncogenes and tumor suppressor genes are in fact normal cellular genes with vital functions within normal cells. It is only when they are mutated in some way that these genes become cancer causing.

The Ha-ras gene is a good example of an onco-gene. Located on chromosome 11 at the normal cellular Ha-ras gene is one of a family of ras genes and encodes a small protein that is involved in intracellular signaling. Mutations in the ras oncogenes disrupt processing of cell signals and contribute to cell transformation. Mutations in ras oncogenes are found in approximately 10% of cancers especially cancer of the colon and lung.

The most important tumor suppressor gene is the p53 gene. This gene which is known as the guardian of the genome encodes for a protein with multiple intracellular functions related to the detection of DNA damage. When DNA is damaged by exposure to a mutagen such as UV (ultraviolet) irradiation the p53 gene is expressed. The p53 protein causes the cell to stop dividing so DNA mismatch repair genes can repair the DNA. If the DNA is successfully repaired, the cell resumes normal cell functions and the p53 gene is down regulated. However, if the DNA damage is beyond repair the p53 protein switches on a process called apoptosis (programmed cell death) leading to the death of the cell. For example, sunburn to the skin causes UV induced DNA damage, which often cannot be repaired. Expression of the p53 gene induces apoptosis the skin cells die and peel off.

Mutations in the p53 gene occur in approximately 50% of all cancers—particularly cancer of the breast, colon, lung, and brain. The mutant p53 protein is unable to stop uncontrolled cell division or switch on apoptosis, and can no longer protect the cell from acquiring additional mutation in other genes. The result is an unstable cell genome liable to further progressive DNA damage. The inherited cancer condition, Li-Fraumeni syndrome, is an autosomal dominant disorder caused by inherited mutations in the p53 gene. Individuals affected with Li-Fraumeni syndrome may develop breast cancer, brain tumors, leukemia, prostate cancer and various sarcomas at a young age.

Mismatch repair genes are another class of cancer gene contributing to instability of the cancer cell genome. Damaged DNA is repaired by an active DNA mismatch repair mechanism that identifies damaged DNA, then cuts out and repairs the damaged DNA bases. Mutations in these repair genes are common in cancer cancers of the colon.

Oncogenes, tumor suppressor genes and other cancer causing genes can become mutated in any number of different ways. Most oncogenes become activated by specific mutations within their DNA sequence that causes the gene protein to function abnormally. Some oncogenes such MYCN are activated by DNA amplification. Oncogene amplification occurs commonly in neuroblastoma an aggressive cancer in children. These tumors can acquire hundreds of copies of this gene by DNA amplification making the cancer very resistant to treatment. Another means of oncogene activation is by its translocation from one chromosome to another. In the Burkitt lymphoma the c-myc oncogene is translocated from chromosome 8 to chromosome 14 where it becomes activated by an immunoglobulin gene. Only one allele of an oncogenes need to be activated for it to participate in cell transformation.

Tumor suppressor genes on the other hand are recessive and normally act to suppress cell replication. Cell transformation occurs when both gene alleles are inactivated (knocked out). Most commonly, inactivation of one gene allele occurs by a chromosome deletion. The second event may be an inactivating gene mutation, a second deletion or methylation of the genes promoter.

Regardless of the actual mutations involved, a crucial concept in the development of most cancers is that more than one gene is usually involved in the process. Indeed in the development of cancer of the colon at least six or more separate oncogenes and tumor suppressor genes are involved in a progressive multi-step process to transform a normal colon cell into an aggressive, self replicating and invading cancer.

More recently, the application of gene expression arrays (microarrays) to the study of cancer has found that in addition to multiple gene mutations, the expression of many hundreds of non-mutant genes is affected in the process of cell transformation.

Microarray analysis of cancers of the breast and soft tissues has also identified distinctive patterns of gene expression that can be used to aid diagnosis and predict the clinical behavior of individual tumors.

This type of genetic analysis will also aid the development of new cancer therapies directed specifically at the molecular biology of the cancer.

Types of cancers

There are several different types of cancers:

• Carcinomas are cancers that arise in the epithelium (the layers of cells covering the body’s surface and lining the internal organs and various glands). Ninety percent of human cancers fall into this category. Carcinomas can be subdivided into two subtypes: adenocarcinomas and squamous cell carcinomas. Adenocarcinomas are cancers that develop in an organ or a gland, while squamous cell carcinomas refer to cancers that originate in the skin.
• Melanomas also originate in the skin, usually in the pigment cells (melanocytes).
• Sarcomas are cancers of the supporting tissues of the body, such as bone, muscle and blood vessels.
• Cancers of the blood and lymph glands are called leukemia and lymphomas respectively.
• Gliomas are cancers of the nerve tissue.

Causes and symptoms

The major risk factors for cancer are: tobacco, alcohol, diet, sexual and reproductive behavior, infectious agents, family history, occupation, environment and pollution.

According to the estimates of the American Cancer Society (ACS), just over 40% of the cancer deaths in 2004 were due to tobacco and excessive alcohol use. An additional one-third of the deaths were related to diet and nutrition. Many of the one million skin cancers that each year were due to over-exposure to ultraviolet light from the Sun’s rays.

Tobacco

Eighty to ninety percent of the lung cancer cases occur in smokers. Smoking has also been shown to be a contributory factor in cancers of upper respiratory tract, esophagus, larynx, bladder, pancreas, and probably liver, stomach, and kidney as well. Recently, scientists have also shown that second-hand smoke (or passive smoking) can increase one’s risk of developing cancer.

Alcohol

Excessive consumption of alcohol is a risk factor in certain cancers, such as liver cancer. Alcohol, in combination with tobacco, significantly increases the chances that an individual will develop mouth, pharynx, larynx, and esophageal cancers.

Diet

Thirty five percent of all cancers are due to dietary causes. Excessive intake of fat leading to obesity has been associated with cancers of the breast, colon, rectum, pancreas, prostate, gall bladder, ovaries, and uterus.

Sexual and reproductive behavior

The human papilloma virus, which is sexually transmitted has been shown to cause cancer of the cervix. Having too many sex partners and becoming sexually active early has been shown to increase one’s chances of contracting this disease. In addition, it has also been shown that women who do not have children or have children late in life, have an increased risk for both ovarian and breast cancer.

Infectious agents

In the later decades of the twentieth century, scientists obtained evidence to show that approximately 15% of the world’s cancer deaths can be traced to viruses, bacteria, or parasites. The most common cancer-causing pathogens and the cancers associated with them are shown in table form.

Family history

Certain cancers like breast, colon, ovarian and uterine cancer, recur generation after generation in some families. A few cancers, such as the eye cancer retinoblastoma, a type of colon cancer, and a type of breast cancer known as early-onset breast cancer, have been shown to be linked to certain genes that can be tracked within a family. It is therefore possible that inheriting particular genes makes a person susceptible to certain cancers.

Occupational hazards

There is evidence to prove that certain occupational hazards account for at least 4% of all cancer deaths. For example, asbestos workers have an increased incidence of lung cancer. Similarly, a higher likelihood of getting bladder cancer is associated with dye, rubber and gas workers; skin and lung cancer with smelters, gold miners, and arsenic workers; leukemia with glue and varnish workers; liver cancer with PVC (polyvinyl chloride) manufacturers; and lung, bone and bone marrow cancer with radiologists and uranium miners.

Environment

Radiation is believed to cause 1 to 2% of all cancer deaths. Ultra-violet radiation from the sun accounts for a majority of melanoma deaths. Other sources of radiation are x rays, radon gas, and ionizing radiation from nuclear material.

Pollution

Several studies have shown that there is a well-established link between asbestos and cancer. Chlorination of water may account for a small rise in cancer risk. However, the main danger from pollution occurs when dangerous chemicals from industries escape into the surrounding environment. It has been estimated that approximately 1% of cancer deaths are due to air, land and water pollution.

Cancer is a progressive disease, and goes through several stages. Each stage may produce a number of symptoms. Some symptoms are produced early and may occur due to a tumor that is growing within an organ or a gland. As the tumor grows, it may press on the nearby nerves, organs and blood vessels. This causes pain and some pressure which may be the earliest warning signs of cancer.

Despite the fact that there are several hundred different types of cancers, producing very different symptoms, the ACS has established the following seven symptoms as possible warning signals of cancer:

• Changes in the size, color, or shape of a wart or a mole;
• A sore that does not heal;
• Persistent cough, hoarseness, or sore throat;
• A lump or thickening in the breast or elsewhere;
• Unusual bleeding or discharge;
• Chronic indigestion or difficulty in swallowing; and
• Any change in bowel or bladder habits.

Many other diseases, besides cancer, could produce the same symptoms. However, it is important to have these symptoms checked, as soon as possible, especially if they linger. The earlier a cancer is diagnosed and treated, the better the chance of it being cured. Many cancers such as breast cancer may not have any early symptoms. Therefore, it is important to undergo routine screening tests such as breast self-examinations and mammograms.

Diagnosis

Diagnosis begins with a thorough physical examination and a complete medical history. The doctor will observe, feel, and palpate (apply pressure by touch) different parts of the body in order to identify any variations from the normal size, feel and texture of the organ or tissue.

As part of the physical examination, the doctor will inspect the oral cavity or the mouth. By focusing a light into the mouth, the physician will look for abnormalities in color, moisture, surface texture, or presence of any thickening or sore in the lips, tongue, gums, the hard palate on the roof of the mouth, and the throat. To detect thyroid cancer, the doctor will observe the front of the neck for swelling. He/she may gently manipulate the neck and palpate the front and side surfaces of the thyroid gland (located at the base of the neck) to detect any nodules or tenderness. As part of the physical examination, the doctor will also palpate the lymph nodes in the neck, under the arms and in the groin. Many illnesses and cancers cause a swelling of the lymph nodes.

The doctor may conduct a thorough examination of the skin to look for sores that have been present for more than three weeks and that bleed, ooze, or crust; irritated patches that may itch or hurt, and any change in the size of a wart or a mole.

Examination of the female pelvis is used to detect cancers of the ovaries, uterus, cervix, and vagina. In the visual examination, the doctor looks for abnormal discharges or the presence of sores. Then, using gloved hands the physician palpates the internal pelvic organs such as the uterus and ovaries to detect any abnormal masses. Breast examination includes visual observation where the doctor looks for any discharge, unevenness, discoloration, or scaling. The doctor palpates both breasts to feel for masses or lumps.

For males, inspection of the rectum and the prostate is also included in the physical examination. The doctor inserts a gloved finger into the rectum and rotates it slowly to feel for any growths, tumors, or other abnormalities. The doctor also conducts an examination of the testis, where the doctor observes the genital area and looks for swelling or other abnormalities. The testicles are palpated to identify any lumps, thickening or differences in the size, weight, and firmness.

If the doctor detects an abnormality on physical examination, or the patient has some symptom that could be indicative of cancer, the doctor may order diagnostic tests.

Laboratory studies of sputum (sputum cytology), blood, urine, and stool can detect abnormalities that may indicate cancer. Sputum cytology is a test where the phlegm that is coughed up from the lungs is microscopically examined. It is often used to detect lung cancer. A blood test for cancer is easy to perform, usually inexpensive and risk-free. The blood sample is obtained by a laboratory technician or a doctor, by inserting a needle into a vein and is relatively painless. Blood tests can be either specific or non-specific. Often times, in certain cancers, the cancer cells release particular proteins (called tumor markers) and blood tests can be used to detect the presence of these tumor markers. However, with a few exceptions, tumor markers are not used for routine screening of cancers, because several non-cancerous conditions also produce positive results. Blood tests are generally more useful in monitoring the effectiveness of the treatment, or in following the course of the disease and detecting recurrent disease.

Imaging tests such as computed tomography (CT) scans, magnetic resonance imaging (MRI), ultrasound, and fiberoptic scope examinations help the doctors determine the location of the tumor even if it is deep within the body. Conventional x-rays are often used for initial evaluation, because they are relatively cheap, painless, and easily accessible. In order to increase the information obtained from a conventional x ray, air or a dye (such as barium or iodine) may be used as a contrast medium to outline or highlight parts of the body.

The most definitive diagnostic test is the biopsy, wherein a piece of tissue is surgically removed for microscope examination. Besides, confirming a cancer, the biopsy also provides information about the type of cancer, the stage it has reached, the aggressiveness of the cancer and the extent of its spread. Since a biopsy provides the most accurate analysis, it is considered the gold standard of diagnostic tests.

Screening examinations, conducted regularly by healthcare professionals can result in the detection of cancers of the breast, colon, rectum, cervix, prostate, testis, tongue, mouth, and skin at early stages, when treatment is more likely to be successful. Some of the routine screening tests recommended by the ACS are sigmoidoscopy (for colorectal cancer), mammography (for breast cancer), pap smear (for cervical cancer), and the PSA (prostate-specific antigen) test (for prostate cancer). Self-examinations for cancers of the breast, testes, mouth and skin can also help in detecting the tumors before the symptoms become serious.

A recent revolution in molecular biology and cancer genetics has contributed a great deal to the development of several tests designed to assess one’s risk of getting cancers. These new techniques include genetic testing, where molecular probes are used to identify mutations in certain genes that have been linked to particular cancers.

Treatment

The aim of cancer treatment is to remove all or as much of the tumor as possible and to prevent the recurrence or spread of the primary tumor. While devising a treatment plan for cancer, the likelihood of curing the cancer has to be weighed against the side effects of the treatment. If the cancer is very aggressive and a cure is not possible, then the treatment should be aimed at relieving the symptoms and controlling the cancer for as long as possible.

Cancer treatment can take many different forms, and it is always tailored to the individual patient. The decision on which type of treatment is the most appropriate depends on the type and location of cancer, the extent to which it has already spread, the patient’s age, sex, general health status and personal treatment preferences. The major types of treatment are: surgery, radiation, chemotherapy, immunotherapy, hormone therapy, and bone-marrow transplantation.

Surgery

Surgery is the removal of a visible tumor and is the most frequently used cancer treatment. It is most effective when a cancer is small and confined to one area of the body.

Surgery can be used for many purposes. The following list describes the major reasons.

• Treatment: Treatment of cancer by surgery involves removal of the tumor to cure the disease. This is typically done when the cancer is localized to a discrete area. Along with the cancer, some part of the normal surrounding tissue is also removed to ensure that no cancer cells remain in the area. Since cancer usually spreads via the lymphatic system, adjoining lymph nodes may be examined and sometimes they are removed as well.
• Preventive surgery: Preventive or prophylactic surgery involves removal of an abnormal looking area that is likely to become malignant over time. For example, about 40% of the people with a colon disease known as ulcerative colitis, ultimately die of colon cancer. Rather than live with the fear of developing colon cancer, these people may choose to have their colons removed and reduce the risk significantly.
• Diagnostic purposes: The most definitive tool for diagnosing cancer is a biopsy. Sometimes a biopsy can be performed by inserting a needle through the skin. However, at other times, the only way to obtain some tissue sample for biopsy, is by performing a surgical operation.
• Cytoreductive surgery: is a procedure where the doctor removes as much of the cancer as possible, and then treats the remaining with radiation therapy or chemotherapy or both.
• Palliative surgery: is aimed at curing the symptoms, not the cancer. Usually, in such cases, the tumor is so large or has spread so much that removing the entire tumor is not an option. For example, a tumor in the abdomen may be so large, that it may press on and block a portion of the intestine, interfering with digestion and causing pain and vomiting. Debulking surgery may remove a part of the blockage and relieve the symptoms. In tumors that are dependent on hormones, removal of the organs that secrete the hormones is an option. For example, in prostate cancer, the release of testosterone by the testicles stimulates the growth of cancerous cells. Hence, a man may undergo an orchiectomy (removal of testicles) to slow the progress of the disease. Similarly, in a type of aggressive breast cancer, removal of the ovaries (oophorectomy) in women will stop the synthesis of hormones from the ovaries and slow the progression of the cancer.

Radiation

Radiation kills cells. Radiation is used alone in cases where a tumor is unsuitable for surgery. More often, it is used in conjunction with surgery and chemotherapy. Radiation can be either external or internal. In the external form, the radiation is aimed at the tumor from outside the body. In internal radiation (also known as brachytherapy), a radioactive substance, in the form of pellets or liquid is placed at the cancerous site by means of a pill, injection, or insertion in a sealed container.

Chemotherapy

Chemotherapy is the use of drugs to more specifically kill cancer cells. It destroys the hard-to-detect cancer cells that have spread and are circulating in the body. Chemotherapeutic drugs can be taken either orally (by mouth) or intravenously, and may be given alone or in conjunction with surgery, radiation, or both.

When chemotherapy is used before surgery or radiation, it is known as primary chemotherapy or neoadjuvant chemotherapy. An advantage of neoadjuvant chemotherapy is that since the cancer cells have not been exposed to anti-cancer drugs, they are especially vulnerable. It can therefore be used effectively to reduce the size of the tumor for surgery or target it for radiation. However, the toxic effects of neoadjuvant chemotherapy are severe. In addition, it may make the body less tolerant to the side effects of other treatments that follow such as radiation therapy. The more common use of chemotherapy is adjuvant therapy, which is given to enhance the effectiveness of other treatments For example, after surgery, adjuvant chemotherapy is given to destroy any cancerous cells that still remain in the body.

Immunotherapy

Immunotherapy uses the body’s own immune system to destroy cancer cells. This form of treatment is being intensively studied in clinical trials and is not yet widely available to most cancer patients. The various immunological agents being tested include substances produced by the body (such as the interferons, inter-leukins, and growth factors), monoclonal antibodies, and vaccines. Unlike traditional vaccines, cancer vaccines do not prevent cancer. Instead, they are designed to treat people who already have the disease. Cancer vaccines work by boosting the body’s immune system and training the immune cells to specifically destroy cancer cells.

Hormone therapy

Hormone therapy is standard treatment for some types of cancers that are hormone-dependent and grow faster in the presence of particular hormones. These include cancer of the prostate, breast, and uterus. Hormone therapy involves blocking the production or action of these hormones. As a result the growth of the tumor slows down and survival may be extended for several months or years.

Bone marrow transplantation

The bone marrow is the tissue within the bone cavities that contains blood-forming cells. Healthy bone marrow tissue constantly replenishes the blood supply and is essential to life. Sometimes, the amount of drugs or radiation needed to destroy cancer cells also destroys bone marrow. Replacing the bone marrow with healthy cells counteracts this adverse effect. A bone marrow transplant is the removal of marrow from one person and the transplant of the blood-forming cells either to the same person or to some one else. Bone-marrow transplantation, while not a therapy in itself, is often used to rescue a patient, by allowing those with cancer to undergo very aggressive therapy.

Many different specialists generally work together as a team to treat cancer patients. An oncologist is a physician who specializes in cancer care. The oncologist provides chemotherapy, hormone therapy, and any other non-surgical treatment that does not involve radiation. The oncologist often serves as the primary physician and coordinates the patient’s treatment plan.

The radiation oncologist specializes in using radiation to treat cancer, while the surgical oncologist performs the operations needed to diagnose or treat cancer. Gynecologist-oncologists and pediatric-oncologists, as their titles suggest, are physicians involved with treating women’s and children’s cancers respectively. Many other specialists may also be involved in the care of a cancer patient. For example, radiologists specialize in the use of x-rays, ultrasounds, CT scans, MRIs, and other techniques that are used to diagnose cancer. Hematologists specialize in disorders of the blood and are consulted in case of blood cancers and bone marrow cancers. The samples that are removed for biopsy are sent to a laboratory, where a pathologist examines them to determine the type of cancer and extent of the disease. Only some of the specialists who are involved with cancer care have been mentioned above. There are many other specialties, and virtually any type of medical or surgical specialist may become involved with care of the cancer patient should it become necessary.

Alternative treatment

There are a multitude of alternative treatments available to help the person with cancer. They can be used in conjunction with, or separate from, surgery, chemotherapy, and radiation therapy. Alternative treatment of cancer is a complicated arena and a trained health practitioner should be consulted.

The effectiveness of complementary therapies such as acupuncture in alleviating cancer pain has not been clinically proven. Bodywork therapies such as massage and reflexology ease muscle tension and may alleviate the side effects such as nausea and vomiting. Homeopathy and herbal remedies used in Chinese traditional herbal medicine have also been reported to alleviate some of the side effects of radiation and chemotherapy and are being recommended by many doctors.

Certain foods including many vegetables, fruits, and grains are believed to offer protection against various cancers. However, isolation of the individual constituent of vegetables and fruits that are anti-cancer agents has proven difficult. In laboratory studies, vitamins such as A, C and E, as well as compounds such as isothiocyanates and dithiolthiones found in broccoli, cauliflower, and cabbage, and beta-carotene found in carrots have been shown to protect against cancer. Studies have shown that eating a diet rich in fiber as found in fruits and vegetables reduces the risk of colon cancer. Exercise and a low fat diet help control weight and reduce the risk of endometrial, breast, and colon cancer.

Certain drugs, which are currently being used for treatment, could also be suitable for prevention. For example, the drug tamoxifen (Nolvadex^®), that has been very effective against breast cancer, is currently being tested by the National Cancer Institute, for its ability to prevent cancer. Similarly, retinoids derived from vitamin A are being tested for their ability to slow the progression or prevent head and neck cancers. Certain studies have suggested that cancer incidence is lower in areas where soil and foods are rich in the mineral selenium. More trials are needed to explain these intriguing connections.

Prognosis

Life-time risk is the term that cancer researchers use to refer to the probability that an individual, over the course of a lifetime will develop cancer or die from it. In the United States, men have a 1 in 2 lifetime risk of developing cancer, and for women the risk is 1 in 3. Overall, African-Americans are more likely to develop cancer than whites. African-Americans are also 30% more likely to die of cancer than whites.

Many cancers are curable if detected and treated at their early stages. A cancer patient’s prognosis is affected by many factors, particularly the type of cancer the patient has, the stage of the cancer, the extent to which it has metastasized and the aggressiveness of the cancer. In addition, the patient’s age, general health status, and the effectiveness of the treatment being pursued are also important factors.

KEY TERMS

Benign— A growth that does not spread to other parts of the body. Recovery is favorable with treatment.

Biopsy— The surgical removal of a small part of a tumor. The excised tissue is studied under the microscope to determine whether it is benign or malignant.

Bone marrow— A spongy tissue located in the hollow centers of certain bones, such as the skull and hip bones. Bone marrow is the site of blood cell generation.

Carcinogen— Any substance capable of causing cancer by mutating the cell’s DNA.

Chemotherapy— Use of powerful drugs to kill cancer cells in the human body.

Epithelium— The layer of cells that covers external and internal surfaces of the body. The many types of epithelium range from flat cells to long cells to cubed cells.

Hormone therapy— Treatment of cancer by inhibiting the production of hormones, such as testosterone and estrogen.

Immunotherapy— Treatment of cancer by stimulating the body s immune defense system.

Malignant— A general term for cells that can dislodge from the original tumor, invade and destroy other tissues and organs.

Metastasis— The spread of cancer from one part of the body to another.

Radiation therapy— Treatment using high-energy radiation from x-ray machines, cobalt, radium, or other sources.

Sore— An open wound or a bruise or lesion on the skin.

Tumor— An uncontrolled growth of tissue, either benign (noncancerous) or malignant (cancerous).

X ray— Electromagnetic radiation of very short wavelength, and very high energy.

To help predict the future course and outcome of the disease and the likelihood of recovery from the disease, doctors often use statistics. The five-year survival rates are the most common measures used. The number refers to the proportion of people with cancer who are expected to be alive, five years after initial diagnosis, compared with a similar population that is free of cancer. It is important to note that while statistics can give some information about the average survival experience of cancer patients in a given population, it cannot be used to indicate individual prognosis, because no two patients are exactly alike.

Prevention

According to nutritionists and epidemiologists from leading universities in the United States, a person can reduce the chances of getting cancer by following some simple guidelines:

• Eating plenty of vegetables and fruits,
• Exercising regularly,
• Avoiding excessive weight gain,
• Avoiding tobacco (including second hand smoke),
• Avoiding excessive amounts of alcohol,
• Avoiding the midday sun (between 11 a.m. and 3 p.m.) when the sun’s rays are the strongest,
• Avoiding risky sexual practices, and
• Avoiding known carcinogens in the environment or work place.

In addition, a vaccine (Guardasil) is now (as of 2007) available for young women against HPV (human papilloma virus). HPV infection is responsible for the eventual development of over two-thirds of cervical cancer cases.

See also Gene therapy; Immunology; Nuclear medicine; Radioisotopes in medicine; Stem cells.

Resources

BOOKS

Haskell, Charles M. Cancer Treatment, 5th ed. Philadelphia, PA: W.B. Saunders, 2001.

King, Roger, J.B., and Mike W. Robins. Cancer Biology. Harlow, UK, and New York: Pearson/Prentice Hall, 2006.

Rosenbaum, Ernst H. MD, et al. Everyone’s Guide to Cancer Therapy, 4th ed. Riverside, NJ: Andrews McMeel Publishing, 2002.

Souhami, Robert L. Oxford Textbook of Oncology. Oxford, UK, and New York: Oxford University Press, 2002.

Tannock, Ian F., ed. The Basic Science of Oncology. New York: McGraw-Hill Medical Publishing Division, 2005.

PERIODICALS

Brookes, Anthony, “Rethinking Genetic Strategies to Study Complex Diseases,” Trends in Molecular Medicine (November 2001):512–6.

OTHER

National Institutes of Health. “National Cancer Institute. cancer.gov” <http://www.nci.nih.gov/> (accessed November 28, 2006).

Lata Cherath Micheal Sullivan

Cancer

Definition

Cancer is not just one disease, but a large group of almost 100 diseases. Its two main characteristics are uncontrolled growth of the cells in the human body and the ability of these cells to migrate from the original site and spread to distant sites. If the spread is not controlled, cancer can result in death.

Description

One out of every four deaths in the United States is from cancer. It is second only to heart disease as a cause of death in the states. About 1.2 million Americans are diagnosed with cancer annually; more than 500,000 die of cancer annually.

Cancer can attack anyone. Since the occurrence of cancer increases as individuals age, most of the cases are seen in adults, middle-aged or older. Sixty percent of all cancers are diagnosed in people who are older than 65 years of age. The most common cancers are skin cancer, lung cancer, colon cancer, breast cancer (in women), and prostate cancer (in men). In addition, cancer of the kidneys, ovaries, uterus, pancreas, bladder, rectum, and blood and lymph node cancer (leukemias and lymphomas) are also included among the 12 major cancers that affect most Americans.

Cancer, by definition, is a disease of the genes. A gene is a small part of DNA, which is the master molecule of the cell. Genes make "proteins," which are the ultimate workhorses of the cells. It is these proteins that allow our bodies to carry out all the many processes that permit us to breathe, think, move, etc.

Throughout people's lives, the cells in their bodies are growing, dividing, and replacing themselves. Many genes produce proteins that are involved in controlling the processes of cell growth and division. An alteration (mutation) to the DNA molecule can disrupt the genes and produce faulty proteins. This causes the cell to become abnormal and lose its restraints on growth. The abnormal cell begins to divide uncontrollably and eventually forms a new growth known as a "tumor" or neoplasm (medical term for cancer meaning "new growth").

In a healthy individual, the immune system can recognize the neoplastic cells and destroy them before they get a chance to divide. However, some mutant cells may escape immune detection and survive to become tumors or cancers.

Tumors are of two types, benign or malignant. A benign tumor is not considered cancer. It is slow growing, does not spread or invade surrounding tissue, and once it is removed, doesn't usually recur. A malignant tumor, on the other hand, is cancer. It invades surrounding tissue and spreads to other parts of the body. If the cancer cells have spread to the surrounding tissues, even after the malignant tumor is removed, it generally recurs.

A majority of cancers are caused by changes in the cell's DNA because of damage due to the environment. Environmental factors that are responsible for causing the initial mutation in the DNA are called carcinogens, and there are many types.

There are some cancers that have a genetic basis. In other words, an individual could inherit faulty DNA from his parents, which could predispose him to getting cancer. While there is scientific evidence that both factors (environmental and genetic) play a role, less than 10% of all cancers are purely hereditary. Cancers that are known to have a hereditary link are breast cancer, colon cancer, ovarian cancer, and uterine cancer. Besides genes, certain physiological traits could be inherited and could contribute to cancers. For example, inheriting fair skin makes a person more likely to develop skin cancer, but only if he or she also has prolonged exposure to intensive sunlight.

There are several different types of cancers:

• Carcinomas are cancers that arise in the epithelium (the layer of cells covering the body's surface and lining the internal organs and various glands). Ninety percent of human cancers fall into this category. Carcinomas can be subdivided into two types: adenocarcinomas and squamous cell carcinomas. Adenocarcinomas are cancers that develop in an organ or a gland, while squamous cell carcinomas refer to cancers that originate in the skin.
• Melanomas also originate in the skin, usually in the pigment cells (melanocytes).
• Sarcomas are cancers of the supporting tissues of the body, such as bone, muscle and blood vessels.
• Cancers of the blood and lymph glands are called leukemias and lymphomas respectively.
• Gliomas are cancers of the nerve tissue.

Causes and symptoms

The major risk factors for cancer are: tobacco, alcohol, diet, sexual and reproductive behavior, infectious agents, family history, occupation, environment and pollution.

JANETD. ROWLEY (1925–)

Janet Davison Rowley was born in New York City on April 5, 1925, to Ethel Mary (Ballantyne) and Hurford Henry Davison. Rowley attended the University of Chicago, earning her B.S. degree in 1946 and her M.D. degree in 1948. She also married Donald A. Rowley in 1948, and the couple ultimately had four sons. Rowley completed both her internship and residency at Chicago hospitals before returning to the University of Chicago Medical School where she conducted research from 1962–1969. She became an associate professor, and finally, in 1977, earned her position as a full professor.

Rowley's research has focused on understanding cancer, with special emphasis on its cytogenetic causes. Her development and use of Giemsa and quinacrine stains enabled Rowley to discover oncogenes and to ultimately show a consistent shifting or translocation of genetic material in chronic myeloid leukemia cells. Rowley's discoveries and continued research have shown that malignant cells in humans undergo this translocation and deletion of genes that cause tumors to grow. Her research has given oncologists new pathways to explore concerning gene therapies for the treatment of cancer.

Co-editor and co-founder of the journal, Genes, Chromosomes and Cancer, Rowley has published an abundance of materials including Chromosome Changes in Leukemia (1978), Genes and Cancer (1984), and Advances in Understanding Genetic Changes in Cancer (1992). Rowley has also received many awards and honors for her work and research.

According to estimates of the American Cancer Society (ACS), approximately 40% of cancer deaths in 1998 were due to tobacco and excessive alcohol use. An additional one-third of the deaths were related to diet and nutrition. Many of the one million skin cancers diagnosed in 1998 were due to over-exposure to ultraviolet light from the sun's rays.

Tobacco

Eighty to 90% of lung cancer cases occur in smokers. Smoking has also been shown to be a contributory factor in cancers of upper respiratory tract, esophagus, larynx, bladder, pancreas, and probably liver, stomach, breast, and kidney as well. Recently, scientists have also shown that second-hand smoke (or passive smoking) can increase one's risk of developing cancer.

Alcohol

Excessive consumption of alcohol is a risk factor in certain cancers, such as liver cancer. Alcohol, in combination with tobacco, significantly increases the chances that an individual will develop mouth, pharynx, larynx, and esophageal cancers.

Diet

Thirty-five percent of all cancers are due to dietary causes. Excessive intake of fat leading to obesity has been associated with cancers of the breast, colon, rectum, pancreas, prostate, gall bladder, ovaries, and uterus.

Sexual and reproductive behavior

The human papillomavirus, which is sexually transmitted, has been shown to cause cancer of the cervix. Having too many sex partners and becoming sexually active early has been shown to increase one's chances of contracting this disease. In addition, it has also been shown that women who don't have children or have children late in life have an increased risk for both ovarian and breast cancer.

Infectious agents

In the last 20 years, scientists have obtained evidence to show that approximately 15% of the world's cancer deaths can be traced to viruses, bacteria, or parasites. The most common cancer-causing pathogens and the cancers associated with them are shown in table form.

Family history

Certain cancers like breast, colon, ovarian, and uterine cancer recur generation after generation in some families. A few cancers, such as the eye cancer "retinoblastoma," a type of colon cancer, and a type of breast cancer known as "early-onset breast cancer," have been shown to be linked to certain genes that can be tracked within a family. It is therefore possible that inheriting particular genes makes a person susceptible to certain cancers.

Occupational hazards

There is evidence to prove that certain occupational hazards account for 4% of all cancer deaths. For example, asbestos workers have an increased incidence of lung cancer. Similarly, a higher likelihood of getting bladder cancer is associated with dye, rubber and gas workers; skin and lung cancer with smelters, gold miners and arsenic workers; leukemia with glue and varnish workers; liver cancer with PVC manufacturers; and lung, bone and bone marrow cancer with radiologists and uranium miners.

Environment

Radiation is believed to cause 1-2% of all cancer deaths. Ultra-violet radiation from the sun accounts for a majority of melanoma deaths. Other sources of radiation are x rays, radon gas, and ionizing radiation from nuclear material.

Pollution

Several studies have shown that there is a well-established link between asbestos and cancer. Chlorination of water may account for a small rise in cancer risk. However, the main danger from pollution occurs when dangerous chemicals from the industries escape into the surrounding environment. It has been estimated that 1% of cancer deaths are due to air, land, and water pollution.

Cancer is a progressive disease, and goes through several stages. Each stage may produce a number of symptoms. Some symptoms are produced early and may occur due to a tumor that is growing within an organ or a gland. As the tumor grows, it may press on the nearby nerves, organs, and blood vessels. This causes pain and some pressure which may be the earliest warning signs of cancer.

Despite the fact that there are several hundred different types of cancers, producing very different symptoms, the ACS has established the following seven symptoms as possible warning signals of cancer:

• changes in the size, color, or shape of a wart or a mole
• a sore that does not heal
• persistent cough, hoarseness, or sore throat
• a lump or thickening in the breast or elsewhere
• unusual bleeding or discharge
• chronic indigestion or difficulty in swallowing
• any change in bowel or bladder habits

Many other diseases, besides cancer, could produce the same symptoms. However, it is important to have these symptoms checked, as soon as possible, especially if they linger. The earlier a cancer is diagnosed and treated, the better the chance of it being cured. Many cancers such as breast cancer may not have any early symptoms. Therefore, it is important to undergo routine screening tests such as breast self-exams and mammograms.

Diagnosis

Diagnosis begins with a thorough physical examination and a complete medical history. The doctor will observe, feel and palpate (apply pressure by touch) different parts of the body in order to identify any variations from the normal size, feel, and texture of the organ or tissue.

As part of the physical exam, the doctor will inspect the oral cavity, or the mouth. By focusing a light into the mouth, he will look for abnormalities in color, moisture, surface texture, or presence of any thickening or sore in the lips, tongue, gums, the hard palate on the roof of the mouth, and the throat. To detect thyroid cancer, the doctor will observe the front of the neck for swelling. He may gently manipulate the neck and palpate the front and side surfaces of the thyroid gland (located at the base of the neck) to detect any nodules or tenderness. As part of the physical examination, the doctor will also palpate the lymph nodes in the neck, under the arms and in the groin. Many illnesses and cancers cause a swelling of the lymph nodes.

The doctor may conduct a thorough examination of the skin to look for sores that have been present for more than three weeks and that bleed, ooze, or crust; irritated patches that may itch or hurt, and any change in the size of a wart or a mole.

Examination of the female pelvis is used to detect cancers of the ovaries, uterus, cervix, and vagina. In the visual examination, the doctor looks for abnormal discharges or the presence of sores. Then, using gloved hands the physician palpates the internal pelvic organs such as the uterus and ovaries to detect any abnormal masses. Breast examination includes visual observation where the doctor looks for any discharge, unevenness, discoloration, or scaling. The doctor palpates both breasts to feel for masses or lumps.

For males, inspection of the rectum and the prostate is also included in the physical examination. The doctor inserts a gloved finger into the rectum and rotates it slowly to feel for any growths, tumors, or other abnormalities. The doctor also conducts an examination of the testes, where the doctor observes the genital area and looks for swelling or other abnormalities. The testicles are palpated to identify any lumps, thickening or differences in the size, weight and firmness.

If the doctor detects an abnormality on physical examination, or the patient has some symptom that could be indicative of cancer, the doctor may order diagnostic tests.

Laboratory studies of sputum (sputum cytology), blood, urine, and stool can detect abnormalities that may indicate cancer. Sputum cytology is a test where the phlegm that is coughed up from the lungs is microscopically examined. It is often used to detect lung cancer. A blood test for cancer is easy to perform, usually inexpensive and risk-free. The blood sample is obtained by a lab technician or a doctor by inserting a needle into a vein and is relatively painless. Blood tests can be either specific or non-specific. Often, in certain cancers, the cancer cells release particular proteins (called tumor markers ) and blood tests can be used to detect the presence of these tumor markers. However, with a few exceptions, tumor markers are not used for routine screening of cancers, because several non-cancerous conditions also produce positive results. Blood tests are generally more useful in monitoring the effectiveness of the treatment, or in following the course of the disease and detecting recurrent disease.

Imaging tests such as computed tomography scans (CT scans), magnetic resonance imaging (MRI), ultrasound and fiberoptic scope examinations help the doctors determine the location of the tumor even if it is deep within the body. Conventional x rays are often used for initial evaluation, because they are relatively cheap, painless and easily accessible. In order to increase the information obtained from a conventional x ray, air or a dye (such as barium or iodine) may be used as a contrast medium to outline or highlight parts of the body.

The most definitive diagnostic test is the biopsy, wherein a piece of tissue is surgically removed for microscope examination. Besides confirming a cancer, the biopsy also provides information about the type of cancer, the stage it has reached, the aggressiveness of the cancer and the extent of its spread. Since a biopsy provides the most accurate analysis, it is considered the gold standard of diagnostic tests.

Screening examinations conducted regularly by healthcare professionals can result in the detection of cancers of the breast, colon, rectum, cervix, prostate, testis, tongue, mouth, and skin at early stages, when treatment is more likely to be successful. Some of the routine screening tests recommended by the ACS are sigmoidoscopy (for colorectal cancer), mammography (for breast cancer), pap smear (for cervical cancer ), and the PSA test (for prostate cancer). Self-examinations for cancers of the breast, testes, mouth, and skin can also help in detecting the tumors before the symptoms become serious.

A recent revolution in molecular biology and cancer genetics has contributed a great deal to the development of several tests designed to assess one's risk of getting cancers. These new techniques include genetic testing, where molecular probes are used to identify mutations in certain genes that have been linked to particular cancers. At present, however, there are a lot of limitations to genetic testing and its utility appears ambiguous, emphasizing the need to develop better strategies for early detection.

Treatment

Treatment and prevention of cancers continue to be the focus of a great deal of research. In 2003, research into new cancer therapies included cancertargeting gene therapy, virus therapy, and a drug that stimulated apoptosis, or self-destruction of cancer cells, but not healthy cells. However, all of these new therapies take years of clinical testing and research.

The aim of cancer treatment is to remove all or as much of the tumor as possible and to prevent the recurrence or spread of the primary tumor. While devising a treatment plan for cancer, the likelihood of curing the cancer has to be weighed against the side effects of the treatment. If the cancer is very aggressive and a cure is not possible, then the treatment should be aimed at relieving the symptoms and controlling the cancer for as long as possible.

Cancer treatment can take many different forms, and it is always tailored to the individual patient. The decision on which type of treatment is the most appropriate depends on the type and location of cancer, the extent to which it has already spread, the patient's age, sex, general health status and personal treatment preferences. The major types of treatment are: surgery, radiation, chemotherapy, immunotherapy, hormone therapy, and bone-marrow transplantation.

Surgery

Surgery is the removal of a visible tumor and is the most frequently used cancer treatment. It is most effective when a cancer is small and confined to one area of the body.

Surgery can be used for many purposes.

• Treatment. Treatment of cancer by surgery involves removal of the tumor to cure the disease. This is typically done when the cancer is localized to a discrete area. Along with the cancer, some part of the normal surrounding tissue is also removed to ensure that no cancer cells remain in the area. Since cancer usually spreads via the lymphatic system, adjoining lymph nodes may be examined and sometimes are removed as well.
• Preventive surgery. Preventive or prophylactic surgery involves removal of an abnormal looking area that is likely to become malignant over time. For example, 40% of people with a colon disease known as ulcerative colitis, ultimately die of colon cancer. Rather than live with the fear of developing colon cancer, these people may choose to have their colons removed and reduce the risk significantly.
• Diagnostic purposes. The most definitive tool for diagnosing cancer is a biopsy. Sometimes, a biopsy can be performed by inserting a needle through the skin. However, at other times, the only way to obtain a tissue sample for biopsy is by performing a surgical operation.
• Cytoreductive surgery is a procedure where the doctor removes as much of the cancer as possible, and then treats the remaining area with radiation therapy or chemotherapy or both.
• Palliative surgery is aimed at curing the symptoms, not the cancer. Usually, in such cases, the tumor is so large or has spread so much that removing the entire tumor is not an option. For example, a tumor in the abdomen may be so large that it may press on and block a portion of the intestine, interfering with digestion and causing pain and vomiting. "Debulking surgery" may remove a part of the blockage and relieve the symptoms. In tumors that are dependent on hormones, removal of the organs that secrete the hormones is an option. For example, in prostate cancer, the release of testosterone by the testicles stimulates the growth of cancerous cells. Hence, a man may undergo an "orchiectomy" (removal of testicles) to slow the progress of the disease. Similarly, in a type of aggressive breast cancer, removal of the ovaries (oophorectomy ) will stop the synthesis of hormones from the ovaries and slow the progression of the cancer.

Radiation therapy

Radiation kills tumor cells. Radiation is used alone in cases where a tumor is unsuitable for surgery. More often, it is used in conjunction with surgery and chemotherapy. Radiation can be either external or internal. In the external form, the radiation is aimed at the tumor from outside the body. In internal radiation (also known as brachytherapy), a radioactive substance in the form of pellets or liquid is placed at the cancerous site by means of a pill, injection or insertion in a sealed container.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. It destroys the hard-to-detect cancer cells that have spread and are circulating in the body. Chemotherapeutic drugs can be taken either orally (by mouth) or intravenously, and may be given alone or in conjunction with surgery, radiation or both.

When chemotherapy is used before surgery or radiation, it is known as primary chemotherapy or "neoadjuvant chemotherapy." An advantage of neoadjuvant chemotherapy is that since the cancer cells have not been exposed to anti-cancer drugs, they are especially vulnerable. It can therefore be used effectively to reduce the size of the tumor for surgery or target it for radiation. However, the toxic effects of neoadjuvant chemotherapy are severe. In addition, it may make the body less tolerant to the side effects of other treatments that follow such as radiation therapy. The more common use of chemotherapy is adjuvant therapy, which is given to enhance the effectiveness of other treatments. For example, after surgery, adjuvant chemotherapy is given to destroy any cancerous cells that still remain in the body. In 2003, a new technique was developed to streamline identification of drug compounds that are toxic to cancerous cells but not to healthy cells. The technique identified nine dugs, one of which had never before been identified for use in cancer treatment. Researchers began looking into developing the new drug for possible use.

Immunotherapy

Immunotherapy uses the body's own immune system to destroy cancer cells. This form of treatment is being intensively studied in clinical trials and is not yet widely available to most cancer patients. The various immunological agents being tested include substances produced by the body (such as the interferons, interleukins, and growth factors), monoclonal antibodies, and vaccines. Unlike traditional vaccines, cancer vaccines do not prevent cancer. Instead, they are designed to treat people who already have the disease. Cancer vaccines work by boosting the body's immune system and training the immune cells to specifically destroy cancer cells.

Hormone therapy

Hormone therapy is standard treatment for some types of cancers that are hormone-dependent and grow faster in the presence of particular hormones. These include cancer of the prostate, breast, and uterus. Hormone therapy involves blocking the production or action of these hormones. As a result the growth of the tumor slows down and survival may be extended for several months or years.

Bone marrow transplantation

The bone marrow is the tissue within the bone cavities that contains blood-forming cells. Healthy bone marrow tissue constantly replenishes the blood supply and is essential to life. Sometimes, the amount of drugs or radiation needed to destroy cancer cells also destroys bone marrow. Replacing the bone marrow with healthy cells counteracts this adverse effect. A bone marrow transplant is the removal of marrow from one person and the transplant of the blood-forming cells either to the same person or to someone else. Bone-marrow transplantation, while not a therapy in itself, is often used to "rescue" patients, by allowing those with cancer to undergo aggressive therapy.

Many different specialists generally work together as a team to treat cancer patients. An oncologist is a physician who specializes in cancer care. The oncologist provides chemotherapy, hormone therapy, and any other non-surgical treatment that does not involve radiation. The oncologist often serves as the primary physician and coordinates the patient's treatment plan.

The radiation oncologist specializes in using radiation to treat cancer, while the surgical oncologist performs the operations needed to diagnose or treat cancer. Gynecologist-oncologists and pediatric-oncologists, as their titles suggest, are physicians involved with treating women's and children's cancers respectively. Many other specialists also may be involved in the care of a cancer patient. For example, radiologists specialize in the use of x rays, ultrasounds, CT scans, MRI imaging and other techniques that are used to diagnose cancer. Hematologists specialize in disorders of the blood and are consulted in case of blood cancers and bone marrow cancers. The samples that are removed for biopsy are sent to a laboratory, where a pathologist examines them to determine the type of cancer and extent of the disease. Only some of the specialists who are involved with cancer care have been mentioned above. There are many other specialties, and virtually any type of medical or surgical specialist may become involved with care of the cancer patient should it become necessary.

Alternative treatment

There are a multitude of alternative treatments available to help the person with cancer. They can be used in conjunction with, or separate from, surgery, chemotherapy, and radiation therapy. Alternative treatment of cancer is a complicated arena and a trained health practitioner should be consulted.

Although the effectiveness of complementary therapies such as acupuncture in alleviating cancer pain has not been clinically proven, many cancer patients find it safe and beneficial. Bodywork therapies such as massage and reflexology ease muscle tension and may alleviate side effects such as nausea and vomiting. Homeopathy and herbal remedies used in Chinese traditional herbal medicine also have been shown to alleviate some of the side effects of radiation and chemotherapy and are being recommended by many doctors.

Certain foods including many vegetables, fruits, and grains are believed to offer protection against various cancers. However, isolation of the individual constituent of vegetables and fruits that are anti-cancer agents has proven difficult. In laboratory studies, vitamins such as A, C and E, as well as compounds such as isothiocyanates and dithiolthiones found in broccoli, cauliflower, and cabbage, and beta-carotene found in carrots have been shown to protect against cancer. Studies have shown that eating a diet rich in fiber as found in fruits and vegetables reduces the risk of colon cancer. Exercise and a low fat diet help control weight and reduce the risk of endometrial, breast, and colon cancer.

Certain drugs, which are currently being used for treatment, could also be suitable for prevention. For example, the drug tamoxifen (Nolvadex), which has been very effective against breast cancer, is currently being tested by the National Cancer Institute for its ability to prevent cancer. Similarly, retinoids derived from vitamin A are being tested for their ability to slow the progression or prevent head and neck cancers. Certain studies have suggested that cancer incidence is lower in areas where soil and foods are rich in the mineral selenium. More trials are needed to explain these intriguing connections.

Prognosis

"Lifetime risk" is the term that cancer researchers use to refer to the probability that an individual over the course of a lifetime will develop cancer or die from it. In the United States, men have a one in two lifetime risk of developing cancer, and for women the risk is one in three. Overall, African Americans are more likely to develop cancer than whites. African Americans are also 30% more likely to die of cancer than whites.

Most cancers are curable if detected and treated at their early stages. A cancer patient's prognosis is affected by many factors, particularly the type of cancer the patient has, the stage of the cancer, the extent to which it has metastasized and the aggressiveness of the cancer. In addition, the patient's age, general health status and the effectiveness of the treatment being pursued also are important factors.

To help predict the future course and outcome of the disease and the likelihood of recovery from the disease, doctors often use statistics. The five-year survival rates are the most common measures used. The number refers to the proportion of people with cancer who are expected to be alive, five years after initial diagnosis, compared with a similar population that is free of cancer. It is important to note that while statistics can give some information about the average survival experience of cancer patients in a given population, it cannot be used to indicate individual prognosis, because no two patients are exactly alike.

Prevention

According to nutritionists and epidemiologists from leading universities in the United States, a person can reduce the chances of getting cancer by following some simple guidelines:

• eating plenty of vegetables and fruits
• exercising vigorously for at least 20 minutes every day
• avoiding excessive weight gain
• avoiding tobacco (even second hand smoke)
• decreasing or avoiding consumption of animal fats and red meats
• avoiding excessive amounts of alcohol
• avoiding the midday sun (between 11 A.M. and 3 P.M.) when the sun's rays are the strongest
• avoiding risky sexual practices
• avoiding known carcinogens in the environment or work place

KEY TERMS

Benign— Mild, nonmalignant. Recovery is favorable with treatment.

Biopsy— The surgical removal and microscopic examination of living tissue for diagnostic purposes.

Bone marrow— Spongy material that fills the inner cavities of the bones. The progenitors of all the blood cells are produced in this bone marrow.

Carcinogen— Any substance capable of causing cancer by mutating the cell's DNA.

Chemotherapy— Treatment with certain anticancer drugs.

Epithelium— The layer of cells covering the body's surface and lining the internal organs and various glands.

Hormone therapy— Treatment of cancer by inhibiting the production of hormones such as testosterone and estrogen.

Immunotherapy— Treatment of cancer by stimulating the body's immune defense system.

Malignant— A general term for cells and the tumors they form that can invade and destroy other tissues and organs.

Metastasis— The spread of cancer from one part of the body to another.

Radiation therapy— Treatment using high-energy radiation from x-ray machines, cobalt, radium, or other sources.

Sore— An open wound, bruise or lesion on the skin.

Tumor— An abnormal growth resulting from a cell that lost its normal growth control restraints and started multiplying uncontrollably.

X rays— High-energy radiation used in high doses, either to diagnose or treat disease.

In addition, following the advice of physicians in refraining from certain activities or drugs that are proven as risk factors for certain cancers can help lower one's risk. For instance, while physicians have long known a small increased risk for breast cancer was linked to use of HRT, a landmark study released in 2003 proved the risk was greater than thought. The Women's Health Initiative found that even relatively short-term use of estrogen plus progestin is associated with increased risk of breast cancer, diagnosis at a more advanced stage of the disease, and a higher number of abnormal mammograms. The longer a woman used HRT, the more her risk increased.

Resources

BOOKS

Simone, Joseph V. "Oncology: Introduction." In Cecil Textbook of Medicine, edited by Russel L. Cecil, et al. Philadelphia: W.B. Saunders Company, 2000.

PERIODICALS

"HRT Linked to Higher Breast Cancer Risk, Later Diagnosis, Abnormal Mammograms." Women's Health Weekly July 17, 2003: 2.

"New Way to Stop Cancer Cell Growth Described." Gene Therapy Weekly December 12, 2002: 9.

"Researchers Find New Way to Trigger Self-Destruction of Certain Cancer Cells." Biotech Week July 16, 2003: 285.

"Technique Streamlines Search for Anticancer Drugs." Cancer Weekly April 15, 2003: 62.

"Virus Therapy Attacks Cancer Cells." Cancer Weekly July 29, 2003: 50.

ORGANIZATIONS

American Cancer Society. 1599 Clifton Road, N.E. Atlanta, GA 30329 (800) 227-2345. 〈http://www.cancer.org〉.

Cancer Research Institute (National Headquarters). 681, Fifth Avenue, New York, NY 10022 (800) 992-2623. 〈http://www.cancerresearch.org〉.

National Cancer Institute. 9000 Rockville Pike, Building 31, room 10A16, Bethesda, Maryland, 20892 (800) 422-6237. 〈http://wwwicic.nci.nih.gov〉.

Cancer

Definition

Cancer is not just one disease, but a large group of almost 100 diseases. It is a genetic disease, with two main characteristics of uncontrolled growth of the cells in the human body and the ability of those cells to migrate from the original site and spread to distant sites.

Description

One out of every four deaths in the United States is from cancer. It is second only to heart disease as a cause of death in the United States. About 1.2 million Americans are expected to be diagnosed with cancer each year, of which more than 500,000 are diagnosed as terminally ill. Cancer can attack anyone. Since the occurrence of cancer increases as people age, most cases are seen in adults, middle-aged or older. The most common cancers are skin cancer, lung cancer , colon cancer, breast cancer (in women), and prostate cancer (in men). In addition, cancer of the kidneys, ovaries, uterus, pancreas, bladder, rectum, blood (leukemia ), and lymph nodes (lymphoma) are also included among the 12 major cancers that affect most Americans.

Cancer, by definition, is a disease of the genes. A gene is a small part of DNA, which is the master molecule of the cell. Genes make proteins, which are the ultimate workhorses of the cells. It is these proteins, along with other substances, that allow our bodies to carry out the many processes that permit people to breathe, think, move, etc. Many genes produce proteins that are involved in controlling the processes of cell growth and division. An alteration, or mutation, to the DNA molecule can disrupt the genes and produce faulty proteins. This causes the cell to become abnormal and lose its restraints on growth. The abnormal cell begins to divide uncontrollably and eventually forms a new growth known as a tumor or neoplasm (medical term for cancer meaning "new growth"). In a healthy individual, the immune system can recognize the neoplastic cells and destroy them before they get a chance to divide. However, some mutant cells may escape immune detection and survive to become tumors or cancers.

Tumors are of two types, benign or malignant. A benign tumor is slow growing, does not spread or invade surrounding tissue, and once removed, it does not usually recur. A malignant tumor, on the other hand, invades surrounding tissue and has the capacity to spread to other parts of the body. If the cancer cells have spread to the surrounding tissues, then, even after the primary malignant tumor is removed, it generally recurs either locally or to a distant site. A majority of cancers are caused by changes in the cell's DNA because of damage due to the cell's environment. Environmental factors that are responsible for causing the initial mutation in the DNA are called carcinogens, and there are many types. Some cancers also have a genetic basis. In other words, an individual could inherit faulty DNA from a patient's parents, which could predispose the patient to getting cancer. There is also the two "hit" theory, where there is a combination of a genetic mutation and a stimulation of cell division and/or replication, due to environmental circumstances. While this scientific evidence points to both factors (environmental and genetic) playing a role, less than 10% of all cancers are purely hereditary. Cancers that are known to have a hereditary link are breast cancer, colon cancer, ovarian cancer , and uterine cancer . In late 2001, scientists took one step closer to identifying genetic markers that indicate cancer susceptibility. Called "low penetrance genes," these markers are believed to combine to increase risk for cancer.

There are several different types of cancers. Carcinomas are cancers that arise in the epithelium (the layer of cells covering the body's surface and lining the internal organs and various glands). Ninety percent of human cancers fall into this category. Melanomas are cancers that originate in the skin, usually in the pigment cells

(melanocytes). Sarcomas are cancers of the supporting tissues of the body, such as bone, muscle, and blood vessels. Cancers of the blood and lymph glands are called leukemias and lymphomas respectively. Gliomas are cancers of the nerve tissue.

Causes & symptoms

Causes & risk factors

The major risk factors for cancer are: tobacco, alcohol, diet, sexual and reproductive behavior, infectious agents, family history, occupation, environment, and pollution. According to the estimates of the American Cancer Society (ACS), approximately 40% of the cancer deaths in 2003 were due to tobacco and excessive alcohol use. An additional one-third of the deaths were related to diet and nutrition . Many of the one million skin cancer cases were due to overexposure to ultraviolet light from the sun's rays. It should be noted that medical science has not been able to pinpoint many of the exact causes of cancer, but has been able to estimate risk factors and occurrence associated with various agents.

Tobacco. Eighty to ninety percent of lung cancer cases occur in smokers. Smoking has also been shown to be a contributory factor in cancers of the upper respiratory tract, esophagus, larynx, bladder, pancreas, and probably liver, stomach, breast, and kidney, as well. Recently, scientists have also shown that second-hand smoke (or passive smoking) can increase one's risk of developing cancer.

Alcohol. Excessive consumption of alcohol is a risk factor in certain cancers, such as liver cancer. Alcohol, in combination with tobacco, significantly increases the chances that an individual will develop mouth, pharynx, larynx, and esophageal cancers.

Diet. Thirty five percent of all cancers are estimated to be due to dietary causes. Excessive intake of fat leading to obesity has been associated with cancers of the breast, colon, rectum, pancreas, prostate, gall bladder, ovaries, and uterus.

Sexual and reproductive behavior. The human papillomavirus, which is sexually transmitted, has been implicated to cause cancer of the cervix. In addition, it has also been shown that women who have not had children or have children late in life have an increased risk for both ovarian and breast cancer.

Infectious agents. In the last 20 years, scientists have obtained evidence to estimate that 15% of the world's cancer deaths may be traced to viruses, bacteria, or parasites.

Family history. Certain cancers like breast, colon, ovarian, and uterine cancer, recur generation after generation in some families. A few cancers, such as the eye cancer "retinoblastoma," a type of colon cancer, and a type of breast cancer known as "early-onset breast cancer," have been shown to be linked to certain genes that can be tracked within a family. It is therefore possible that inheriting particular genes makes a person susceptible to certain cancers.

Occupational hazards. There is evidence to estimate that certain occupational hazards account for 4% of all cancer deaths. For example, asbestos workers have an increased incidence of lung cancer. Similarly, a higher likelihood of getting bladder cancer is associated with dye, rubber, and gas workers; skin and lung cancer with smelters, gold miners, and arsenic workers; leukemia with glue and varnish workers; liver cancer with PVC manufacturers; and lung, bone, and bone marrow cancer with radiologists and uranium miners.

Environmental radiation. Exposure is believed to cause 1–2% of all cancer deaths. Ultra-violet radiation from the sun accounts for a majority of melanoma deaths. Other sources of radiation are x rays, radon gas, and ionizing radiation from nuclear material.

Pollution. Several studies have shown that there is a well established link between asbestos and cancer. Chlorination of water may account for a small rise in cancer risk. Studies released in 2003 showed that cadmium, a natural metal found in food, water, and cigarette smoke, disturbs a system in our cells essential to preventing cancer. The main danger from pollution occurs when dangerous chemicals from the industries escape into the surrounding environment. It has been estimated that 1% of cancer deaths are due to air, land, and water pollution.

Alternative medicine tends to disagree with conventional medicine about the causes of cancer, claiming that environmental pollution and emotional and psychological factors are major influences upon the disease. Samuel S. Epstein, a professor of Occupational and Environmental Medicine at the University of Illinois and the chairman of the Cancer Prevention Coalition, is one of the strongest critics of the National Cancer Institute and the American Cancer Society (ACS). Epstein tends to echo many of the beliefs of alternative practitioners. He claims that mainstream medicine, driven by politics, profits, and pharmaceutical sales, is not discussing or sufficiently researching some major factors behind cancer, or researching ways of preventing those causes. Epstein asserts that a primary cause of cancer is the massive pollution of the air, water, food, and workplace. For instance, since the 1940s over 100,000 new chemicals have been added to the environment, and each year in the United States alone, over 10 lb (4.5 kg) of pesticides and herbicides per person are used on the food supply, chemicals that are proven to be carcinogenic. Epstein believes that the human immune system simply cannot handle all the new carcinogens and stresses in the environment, and cancer represents this breakdown of the immune system. He is also a critic of some conventional cancer therapies like radiation and chemotherapy, claiming that the therapies themselves are highly carcinogenic and are often responsible for recurrent cancer. Epstein points out that despite the "war on cancer" by mainstream medicine, mortality rates have not been significantly improved by its methods, and more research needs to be dedicated to preventative and alternative measures instead of pharmaceuticals and invasive treatments.

Symptoms

Cancer is a progressive disease, and goes through several stages with varying symptoms. Some symptoms are produced early and may occur due to a tumor that is growing within an organ or a gland. As the tumor grows, it may press on the nearby nerves, organs, and blood vessels.

This causes pain and some pressure that may be the earliest warning signs of cancer. Despite the fact that there are several hundred different types of cancers, producing very different symptoms, the ACS has established the following seven symptoms as possible warning signals of cancer:

• changes in the size, color, or shape of a wart or a mole
• a sore that does not heal
• persistent cough , hoarseness, or sore throat
• a lump or thickening in the breast or elsewhere
• unusual bleeding or discharge
• chronic indigestion or difficulty in swallowing
• any change in bowel or bladder habits

Many other diseases besides cancer, could produce the same symptoms. However, it is important to have these symptoms checked as soon as possible, especially if they linger. The earlier a cancer is diagnosed and treated, the better the chance of it being cured. Many cancers, such as breast cancer, may not have any early symptoms. Therefore, it is important to undergo routine screening tests, such as breast self-exams and mammograms.

Diagnosis

Diagnosis begins with a thorough physical examination and a complete medical history. The doctor will ob serve, feel, and palpate (apply pressure by touch) different parts of the body in order to identify any variations from the normal size, feel, and texture of the organ or tissue. As part of the physical exam, the doctor will inspect the oral cavity, or the mouth. By focusing a light into the mouth, he or she will look for abnormalities in color, moisture, surface texture, or presence of any thickening or soreness in the lips, tongue, gums, the hard palate on the roof of the mouth, and the throat.

To detect thyroid cancer, the doctor will observe the front of the neck for swelling. He may gently manipulate the neck and palpate the front and side surfaces of the thyroid gland (located at the base of the neck) to detect any nodules or tenderness. As part of the physical examination, the doctor will also palpate the lymph nodes in the neck, under the arms, and in the groin. Many illnesses and cancers cause a swelling of the lymph nodes.

The doctor may conduct a thorough examination of the skin to look for sores that have been present for more than three weeks and that bleed, ooze, or crust; irritated patches that may itch or hurt, and any change in the size of a wart or a mole. Examination of the female pelvis is used to detect cancers of the ovaries, uterus, cervix, and vagina. In the visual examination, the doctor looks for abnormal discharges or the presence of sores. Then, using gloved hands the physician palpates the internal pelvic organs such as the uterus and ovaries to detect any abnormal masses. Breast examination includes visual observation where the doctor looks for any discharge, unevenness, discoloration, or scaling. The doctor palpates both breasts to feel for masses or lumps. For males, inspection of the rectum and the prostate is also included in the physical examination. The doctor inserts a gloved finger into the rectum and rotates it slowly to feel for any growths, tumors, or other abnormalities. The doctor also conducts an examination of the testes, where the doctor observes the genital area and looks for swelling or other abnormalities. The testicles are palpated to identify any lumps, thickening, or differences in the size, weight, and firmness.

If the doctor detects an abnormality on physical examination, or the patient has some symptom that could be indicative of cancer, the doctor may order diagnostic tests. Laboratory studies of sputum (sputum cytology), blood, urine, and stool can detect abnormalities that may indicate cancer. Sputum cytology is a test where the phlegm that is coughed up from the lungs is microscopically examined. It is often used to detect lung cancer.

A blood test for cancer is easy to perform, usually inexpensive and risk-free. Blood tests can be either specific or nonspecific. Often times, in certain cancers, the cancer cells release particular proteins (called tumor markers) and blood tests can be used to detect the presence of these tumor markers. However, with a few exceptions, tumor markers are not used for routine screening of cancers, because several noncancerous conditions also produce positive results. Blood tests are generally more useful in monitoring the effectiveness of the treatment, or in following the course of the disease and detecting recurrent disease.

Imaging tests such as computed tomography scans (CT scans), magnetic resonance imaging (MRI), ultra-sound, and fiberoptic scope examinations help doctors determine the location of the tumor even if it is deep within the body. Conventional x rays are often used for initial evaluation, because they are relatively cheap, painless, and easily accessible. In order to increase the information obtained from a conventional x ray, air or a dye (such as barium or iodine ) may be used as a contrast medium to outline or highlight parts of the body.

The most definitive diagnostic test is the biopsy, wherein a piece of tissue is surgically removed for microscope examination. Besides confirming a cancer, the biopsy also provides information about the type of cancer, the stage it has reached, the aggressiveness of the cancer, and the extent of its spread. Since a biopsy provides the most accurate analysis, it is considered the gold standard of diagnostic tests. Screening examinations, conducted regularly by healthcare professionals, can result in the detection of cancers of the breast, colon, rectum, cervix, prostate, testes, tongue, mouth, and skin at early stages, when treatment is more likely to be successful. Some of the routine screening tests recommended by the ACS are sigmoidoscopy (for colorectal cancer ), mammography (for breast cancer), pap smear (for cervical cancer), and the PSA test (for prostate cancer). Self-examinations for cancers of the breast, testes, mouth, and skin can also help in detecting the tumors before the symptoms become serious.

Diagnosis in alternative treatment often relies on conventional diagnostic tools for determining the type and stage of cancer, but will supplement those tools with diagnostic techniques that strive to evaluate the overall health of a person, in order to treat a person holistically. For instance, Ayurvedic medicine and traditional Chinese medicine place high priorities during diagnosis on the patient's emotional and psychological history, as well as considerations like lifestyle, relationships, and the degree of social and spiritual support, in order to have insight into the cause and proper treatment of a particular cancer. These alternative practices also have highly developed diagnostic techniques for the body, including pulse diagnosis ; methods of analyzing the tongue, eyes, skin, hair, and fingernails; palpating and finding problems in the organs and abdomen; and listening to the breath for clues to the internal environment.

Treatment

Choosing an alternative cancer treatment

There are a multitude of alternative treatments available to help a person with cancer. They are usually integrated with allopathic treatments like surgery, chemotherapy, and radiation therapy, where only an estimated 4% exclusively use alternative medicine. Chemotherapy and radiation treatments are some of the most painful and toxic of conventional treatments, and often have unpredictable results. As a rule, alternative treatments are less invasive, nontoxic, and have minimal side effects. When used as adjuncts to conventional treatment, some alternative treatments have been shown to decrease pain and side effects, aid in the recovery process, and improve the quality of life of cancer patients.

Alternative treatment of cancer is a complicated arena and choosing one from the many can seem a difficult task, as can choosing an alternative practitioner. Patients should consult as many trained health practitioners as feasible when choosing alternative therapies. If patients are willing to ask questions and thoroughly re-search their options, they can increase their chances of getting the best possible alternative support for the difficult task of treating cancer.

When choosing alternative treatment, individuals should evaluate practitioners, therapies, and services delivered by clinics or practitioners, as well as the extent of documentation and published literature regarding these concerns. When looking for practitioners, patients should evaluate their training and credentials and their reputations in the healing community. Referrals from other patients should be requested. Furthermore, they should seek practitioners who are knowledgeable and familiar with a broad spectrum of options of treating cancer, including those used by conventional medicine, and who are willing to work in conjunction with conventional doctors if the patient and treatment requires it. Conversely, if patients choose a physician who employs and recommends conventional, allopathic methods, that physician should be willing to communicate with patients, as well as communicate with an alternate provider. Another major consideration when choosing a practitioner is whether he or she seems trustworthy, ethical, and compassionate.

Patients should also evaluate the particular therapy offered by a practitioner or clinic. They should find out exactly how the therapy works and the principles behind it; whether it is harmless or potentially damaging, and the positive benefits it offers; what literature and scientific studies exist for the therapy; and what other patients say about the treatment.

Finally, patients should evaluate the quality of service that the practitioner or clinic offers. Cost, reputation, quality of support personnel, and attention to individual needs are important considerations when evaluating the service dimension of a treatment.

Types of alternative treatment

Alternative medicine generally views cancer as a holistic problem. That is, cancer represents a problem with the body's overall health and immunity. As such, treatment is holistic as well, striving to strengthen and heal the physical, mental, and spiritual aspects of patients. Alternative cancer treatments may emphasize different basic approaches, which include traditional medicines, psychological approaches, nutritional and dietary approaches, physical approaches, integrated approaches, and experimental programs.

TRADITIONAL MEDICINES. Traditional Chinese medicine uses acupuncture, acupressure massage, herbal remedies, and movement therapies like t'ai chi and qigong to treat cancer. Traditional Chinese herbal remedies have already contributed a significant number of anticancer drugs, as studies have shown their anti-cancer properties and immune stimulants. A 2001 report noted that the ancient compound artemisinin (worm-wood ) appears surprisingly effective in targeting certain cancer cells and helping to destroy them. The therapy is much less expensive than many traditional options, but further study was underway. Acupuncture has been shown to reduce some tumors and significantly reduce pain and improve immune system activity.

Ayurvedic medicine utilizes detoxification , herbal remedies, massage, exercise, yoga , breathing techniques, and meditation as part of its cancer treatment. Panchakarma is an extensive detoxification and strengthening program that is recommended for cancer sufferers and those undergoing chemotherapy and radiation. Panchakarma uses fasting , special vegetarian diets , enemas, massage, herbal medicines, and other techniques to rid the body of excess toxins that are believed to contribute to chronic diseases like cancer, and to strengthen the immune system. Ayurvedic herbs are also being demonstrated to have significant anticancer properties.

Naturopathy and homeopathy are traditional Western healing systems using herbal medicines and other techniques to strengthen the immune system and reduce the pain of cancer treatment. Western herbalism is also beginning to compile studies of many herbs that have anticancer and immune strengthening properties.

PSYCHOLOGICAL APPROACHES. Alternative treatments that seek to help patients with the mental and spiritual challenges that cancer poses include psychotherapy , support groups, guided imagery , meditation, biofeedback , and hypnosis.

Psychological approaches work with the idea that the mind and emotions can profoundly influence the health of the body and diseases like cancer. Many studies have acknowledged that mind and emotions play a key role in cancer and immune functioning, and psychological approaches are being used by many conventional programs, including Harvard Medical School. A new field of academic medicine called psychoneuroimmunology has begun that studies the interactions between mental states and immune response.

Studies have shown that patients who approach their cancer with positive attitudes and peaceful acceptance have higher survival rates than those patients who react with negative emotions, like depression , cynicism, or helplessness. Alternative treatments use psychological approaches to help patients overcome the mental and emotional barriers to healing.

PHYSICAL APPROACHES. Physical approaches to cancer include exercise; massage therapies; movement therapies like yoga, t'ai chi and qigong; breathing techniques; and relaxation techniques. These therapies strive to increase immune system response, promote relaxation and stress reduction, and reduce side effects of conventional treatments such as pain, nausea , weakness, and physical immobility.

NUTRITIONAL AND DIETARY APPROACHES. Diet is now recognized by scientists to play a major role in reducing the risk of some cancers. A 1992 report in Oncology claimed that nutritional factors may account for up to 70% of avoidable cancer mortality in this country. Many nutritionists also state that cancer patients have heightened needs for diets free of toxic chemicals and full of cancer-fighting nutrients. Diet and nutrition can improve both a cancer patient's chances for recovery and quality of life during treatment. In laboratory studies, vitamins such as A, C, and E, as well as compounds such as isothiocyanates and dithiolthiones found in broccoli, cauliflower, and cabbage, and the antioxidant beta-carotene found in carrots, have been shown to protect against cancer. Additionally, bioflavonoids and lycophene found in green tea help in the prevention of cancer.

Dietary approaches for cancer include vegetarianism , raw food diets, macrobiotics, the Gerson diet, and the Livingston-Wheeler nutritional program, discussed below. Cancer diets generally emphasize fresh fruits, vegetables, whole grains, and legumes, and restrict intake of fat, meat, dairy products, sugar, processed foods, and other foods believed to tax cancer patients. Nutritional approaches to cancer include antioxidant and vitamin supplementation and the use of numerous herbal extracts. There are many herbs that have been shown to have anticancer, immune enhancing, and symptom reducing properties, and patients are recommended to consult competent herbalists for herbal support.

INTEGRATED APPROACHES. Keith Block is a conventional physician and oncologist who is integrating many alternative practices into his cancer treatment center affiliated with the Chicago Medical School in Illinois. His program seeks to provide individualized cancer treatment using conventional therapies while integrating alternative healing techniques. Block advocates a special diet (based on vegetarianism and macrobiotics), exercise, psychological support, and herbal and nutritional supplements. Block's program has received acclaim for both treatment success and satisfaction of patients.

EXPERIMENTAL PROGRAMS. Antineoplaston therapy was developed by Stanislaw Burzynski, a Polish physician who began practicing in Houston, Texas. Burzynski has isolated a chemical, deficient in those with cancer, which he believes stops cancer growth, and his treatment has shown some promise.

Dr. Joseph Gold, the director of the Syracuse Cancer Research Institute, discovered that the chemical hydrazine sulfate has many positive effects in cancer patients, including stopping weight loss, shrinking tumors, and increasing survival rates.

The Livingston therapy was developed by the late Dr. Virginia Livingston, an American physician. She asserted that cancer is caused by certain bacteria that she claimed are present in all tumors. She advocated a detoxification program and special diet that emphasized raw or lightly cooked and primarily vegetarian foods, with special vitamin and nutritional supplements.

The Gerson therapy was for years the best known nutritional therapy for cancer. It is available in two clinics in California and Mexico. It consists of a basic vegetarian diet low in salt and fat, with high doses of particular nutrients using raw fruit and vegetable juices. The Gerson therapy also requires patients to drink raw calf's liver juice, believed to aid the liver, and advocates frequent coffee enemas, which are claimed to help the body evacuate toxins.

Allopathic treatment

The aim of allopathic (conventional) cancer treatment is to remove all or as much of the tumor as possible and to prevent the recurrence or spread of the primary tumor. While devising a conventional treatment plan for cancer, the likelihood of curing the cancer has to be weighed against the side effects of the treatment. If the cancer is very aggressive and a cure is not possible, then the treatment should be aimed at relieving symptoms and controlling the cancer for as long as possible. Cancer treatment can take many different forms, and it is always tailored to the individual patient. The decision on which type of treatment is the most appropriate depends on the type and location of cancer, the extent to which it has already spread, the patient's age, sex, general health status, and personal treatment preferences. The major types of treatment are: surgery, radiation, chemotherapy, immunotherapy, hormone therapy, and bone marrow transplantation.

Surgery

Surgery is the removal of a visible tumor and is the most frequently used cancer treatment. It is most effective when a cancer is small and confined to one area of the body. Surgery can be used for many purposes. Treatment of cancer by surgery involves removal of the tumor to cure the disease. Along with the cancer, some part of the normal surrounding tissue may also be removed to ensure that no cancer cells remain in the area. Since cancer usually spreads via the lymphatic system, adjoining lymph nodes may be examined and sometimes removed, as well. Preventive or prophylactic surgery involves removal of an abnormal looking area that is likely to become malignant over time. The most definitive tool for diagnosing cancer is a biopsy. Sometimes a biopsy can be performed by inserting a needle through the skin. However, at other times, the only way to obtain tissue sample for biopsy is by performing a surgical operation.

Radiation

Radiation kills tumor cells. Radiation is used alone in cases where a tumor is unsuitable for surgery. More often, it is used in conjunction with surgery and chemotherapy. Radiation can be either external or internal. In the external form, the radiation is aimed at the tumor from outside the body. In internal radiation (also known as brachytherapy), a radioactive substance in the form of pellets or liquid is placed at the cancerous site by means of a pill, injection, or insertion in a sealed container.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. It destroys the hard-to-detect cancer cells that have spread and are circulating in the body. Chemotherapeutic drugs can be taken either orally or intravenously, and may be given alone or in conjunction with surgery, radiation, or both. The toxic effects of chemotherapy are severe. In 2003, a new technique was developed to streamline identification of drug compounds that are toxic to cancerous cells but not to healthy cells. The technique identified nine drugs, one of which had never before been identified for use in cancer treatment. Researchers began looking into developing the new drug for possible use. In addition, it may make the body less tolerant to the side effects of other treatments that follow, such as radiation therapy. The more common use of chemotherapy is adjuvant therapy, which is given to enhance the effectiveness of other treatments. For example, after surgery, adjuvant chemotherapy is given to destroy any cancerous cells that still remain in the body.

Immunotherapy

Immunotherapy uses the body's own immune system to destroy cancer cells. This form of treatment is being intensively studied in clinical trials and is not yet widely available to most cancer patients. The various immunological agents being tested include substances produced by the body (such as the interferons, interleukins, and growth factors), monoclonal antibodies, and vaccines. Unlike traditional vaccines, cancer vaccines do not prevent cancer. Instead, they are designed to treat people who already have the disease. Cancer vaccines work by boosting the body's immune system and training the immune cells to specifically destroy cancer cells.

Hormone therapy

Hormone therapy is standard treatment for some types of cancers that are hormone-dependent and grow faster in the presence of particular hormones. These include cancer of the prostate, breast, and uterus. Hormone therapy involves blocking the production or action of these hormones. As a result, the growth of the tumor slows down and survival may be extended for several months or years. However, in 2003, the Women's Health Initiative found that even relatively short-term use of estrogen plus progestin is associated with increased risk of breast cancer, diagnosis at a more advanced stage of the disease, and a higher number of abnormal mammograms. The longer a woman used HRT, the more her risk increased. This contradicted earlier beliefs that HRT could prevent breast cancer. So checking with a physician for the latest information is advised.

Bone marrow transplantation

The bone marrow is the tissue within the bone cavities that contains blood-forming cells. Healthy bone marrow tissue constantly replenishes the blood supply and is essential to life. Sometimes, the amount of drugs or radiation needed to destroy cancer cells also unfortunately destroys bone marrow. Replacing the bone marrow with healthy cells counteracts this adverse effect. A bone marrow transplant is the removal of marrow from one person and the transplant of the blood-forming cells either to the same person or to someone else. Bone marrow transplantation, while not a therapy in itself, is often used to rescue a patient, by allowing those with cancer to undergo very aggressive therapy.

In 2001, interest grew in adding hyperthermia to conventional therapy such as radiation. By raising tumors to high fever temperatures, the performance of certain cancer drugs was noted. Hyperthermia is thought to destroy cancer cells much the same way that the body uses fever to naturally combat other forms of disease.

Many different specialists generally work together as a team to treat cancer patients. An oncologist is a physician who specializes in cancer care. The oncologist provides chemotherapy, hormone therapy, and any other non-surgical treatment that does not involve radiation. The oncologist often serves as the primary physician and coordinates the patient's treatment plan. There are many other specialists involved in cancer treatment, and virtually any type of medical or surgical specialist may become involved with care of the cancer patient, should it become necessary.

Expected results

Lifetime risk is the term that cancer researchers use to refer to the probability that an individual, over the course of a lifetime, will develop cancer or die from it. In the United States, men have a one in two lifetime risk of developing cancer, and for women the risk is one in three. Overall, African Americans are more likely to develop cancer than Caucasians. African Americans are also 30% more likely to die of cancer than Caucasians. Many cancers are curable if detected and treated at their early stages. A cancer patient's prognosis is affected by many factors, particularly the type of cancer the patient has, the stage of the cancer, the extent to which it has metastasized, and the aggressiveness of the cancer. In addition, the patient's age, general health status, and the effectiveness of the treatment being pursued are also important factors. To help predict the future course and outcome of the disease and the likelihood of recovery from the disease, doctors often use statistics. The five-year survival rates are the most common measures used. The number refers to the proportion of people with cancer who are expected to be alive five years after initial diagnosis, compared with a similar population that is free of cancer. It is important to note that while statistics can give some information about the average survival experience of cancer patients in a given population, they cannot be used to indicate individual prognosis, because no two patients or cancers are exactly alike. The unpredictability of cancer can be seen as positive, as well as negative—some patients have experienced recoveries in cases that were deemed incurable.

Alternative medicine rarely claims to be able to cure cancer on a regular basis, but many treatments seem to help with controlling symptoms, controlling the pain and side effects of conventional treatments, and increasing the quality of life for cancer sufferers. Alternative therapies have also shown unexpected results and cures. Alternative therapies may be strongest as preventative measures, before major problems like cancer occur in the body.

Prevention

Most practitioners agree that the best treatment for cancer is prevention. Having sound physical and mental health can significantly reduce the chances of getting cancer. The following guidelines are generally recommended by doctors, nutritionists, and alternative practitioners for cancer prevention and recovery:

• Refraining from smoking.
• Not drinking alcohol excessively.
• Exercising regularly, at least 20 minutes per day, preferably outdoors in the fresh air.
• Avoiding exposure to radiation. This includes avoiding unnecessary x rays, not residing near sources of natural or human-made radiation, and avoiding occupational exposure to radiation.
• Avoiding exposure to harmful chemicals in food, the home, and workplace.
• Maintaining proper body weight, particularly avoiding obesity.
• Practicing safe sex.
• Protecting the skin from overexposure to sunlight. Avoiding the midday sun between 11 a.m. and 3 p.m. and never allowing the skin to become sunburned help with prevention.
• Eating a healthy diet. Becoming educated on and practicing dietary principles reduces the risk of cancer. These principles include eating plenty of fresh fruits, vegetables, beans, and whole grains and consuming organically grown foods when possible. Minimizing overeating and reducing intake of meat and dairy products while increasing fiber are recommended. Avoiding processed and canned foods, including soft drinks, and avoiding sugar and refined starch products like white flour also helps. Reducing the intake of fat, avoiding hydrogenated vegetable oils like margarine and shortening, and drinking filtered or spring water have been recommended.
• Striving to maintain sound mental and emotional health is believed to help prevent cancer. Learning a technique like yoga, t'ai chi, meditation, or others can reduce stress and promote relaxation. Maintaining healthy relationships and social support systems also relieves stress.

Resources

BOOKS

Galland, Leo, m.d. The Four Pillars of Healing. New York: Random House, 1997.

Lerner, Michael. Choices in Healing: Integrating the Best of the Conventional and Complementary Approaches to Cancer. Cambridge, Massachusetts: MIT Press, 1994.

Walters, Richard. Options: The Alternative Cancer Therapy Book. New York: Avery Publishing Group, 1993.

Weil, Andrew, m.d. Natural Health, Natural Medicine. New York: Houghton Mifflin, 1995.

Yance, Donald R. Herbal Medicine, Healing and Cancer. Chicago: Keats Publishing, 1999.

PERIODICALS

Alternative Therapies Magazine. PO Box 17969, Durham, NC 27715. (919) 668-8825. http://www.alternative-therapies.com.

"Cadmium Studies Suggest New Pathway to Human Cancer." Drug Week (July 4, 2003): 77.

"HRT Linked to Higher Breast Cancer Risk, Later Diagnosis, Abnormal Mammograms." Women's Health Weekly (July 17, 2003):2.

"Hyperthermia and Hypoxia Spell Cancer Destruction." Cancer Weekly, November 27, 2001: 20.

"Ancient Chinese Folk Remedy may hold Key to Nontoxic Cancer Treatment." Cancer Weekly, December 18, 2001: 12.

"Genetic Identification Techniques Yield Clues to Cancer Susceptibility." Cancer Weekly November 13, 2001: 19.

"Technique Streamlines Search for Anticancer Drugs." Cancer Weekly (April 15, 2003): 62.

ORGANIZATIONS

The Alliance for Alternative Medicine. PO Box 59, Liberty Lake, WA 99019.

American Cancer Society, National Headquarters.1599 Clifton Road, N.E. Atlanta, Georgia 30329 (800) 227-2345. <http://www.cancer.org>.

Cancer Prevention Coalition, c/o University of Illinois School of Public Health, 2121 West Taylor Street Chicago, IL 60612. (312) 996-2297 [email protected]. <http://www.preventcancer.com>.

The Health Resource. 209 Katherine Drive, Conway, AR 72032. (501) 329-5272.

National Cancer Institute. 9000 Rockville Pike, Building 31, room 10A16, Bethesda, MD 20892. (800) 422–6237. <http://www.cancer.gov>.

OTHER

Cancer Nutrition Center. [cited October 2002]. <http://www.cancernutrition.com>.

Douglas Dupler

Teresa G. Odle

Cancer

Cancer is not just one disease , but a large group of almost 100 diseases. Its two main characteristics are uncontrolled growth of the cells in the human body and the ability of these cells to migrate from the original site and spread to distant sites. If the spread is not controlled, cancer can result in death.

One out of every four deaths in the United States is from cancer. It is second only to heart disease as a cause of death in the states. About 1.2 million Americans are expected to be diagnosed with cancer in 1998, of which, more than 500,000 are expected to die.

Cancer can attack anyone. Since the occurrence of cancer increases as individuals age, most of the cases are seen in adults, middle-aged or older. The most common cancers are skin cancer, lung cancer, colon cancer, breast cancer (in women), and prostate cancer (in men). In addition, cancer of the kidneys, ovaries, uterus, pancreas, bladder, rectum, and blood and lymph node cancer (leukemia and lymphomas) are also included among the 12 major cancers that affect most Americans.

The history of cancer as a known disease

The term cancer derives from the observation by Hippocrates in 400 b.c. that the veins radiating from a breast cancer resembled the legs of a crab, hence karkinoma in Greek and cancer in Latin. Cancer is not a single disease, but is many different diseases that all share common biological and pathological characteristics. In most western societies, cancer is a leading cause of death. The disease may develop in any body tissue or organ and over one hundred different types of cancer can occur in adults. Cancer also occurs in children and may even be present at birth .

The first clues to the cause of cancer came over two hundred years ago from an observation by Percivall Pott, a London doctor, who in 1775 found a high incidence of scrotal cancer in men who had worked as chimney sweeps. Later, radiation was found to cause skin cancer and tragically Marie Curie (1867–1934) the discoverer of x rays , died of a cancer caused by prolonged exposure to radiation. During the second half of the twentieth century, epidemiologists (those who study disease in populations) linked exposure to certain environmental toxins and particular types of cancer. Most notably, cigarette smoking and lung cancer, sunlight and skin cancer, and certain industrial chemicals to the cause of bladder and liver cancer. Finally several viruses were also been implicated in causing cancer, such as the hepatitis B virus and cancer of the liver, the Epstein Barr virus and lymphoma, and the human papilloma virus and cancer of the cervix. These important observations all suggested that specific external environmental agents could cause specific cancers.

How then could a diverse range of external agents such as chemicals, radiation and viruses, all lead to the development of cancer? The answer to this question has come over the last 25 years from two different lines of investigation; studies on cancer causing viruses and research into the genetics of some rare cancers in children.

In 1910, Frances Peyton Rous (1879–1970) isolated a virus from a cancer in chickens (a sarcoma) that caused new sarcomas to develop when infected into healthy chickens. Rous's work languished for over 50 years until he was awarded a Nobel Prize in 1966. By this time, methods for the study of viruses and cancer had improved considerably and many new animal derived viruses were found to cause cancer in a range of species . These viruses could also induce cancer-like changes when introduced into normal cells grown in the laboratory. A genetic study of these cancer causing viruses identified a small number of genes termed viral oncogenes (v-oncogenes) which, when introduced into cells, could transform the normal cells into malignant cells.

The presence of viral oncogenes led to the search for endogenous cellular oncogenes, which might cause cancer. In a crucial experiment in the late 1970s, DNA from mouse cells which had been transformed by a chemical carcinogen , was transfected into normal mouse cells. The normal mouse cells became malignant suggesting that a gene within the cancer (a proto-oncogene) had been mutated by exposure to the chemical and was able to induce cancer. Surprisingly, when these endogenous cellular oncogenes were eventually isolated they were found to be homologous to virally derived oncogenes.

In the early 1970s the American pediatrician and scientist, Alfred Knudson at the Fox Chase Cancer Center studied retinoblastoma, a rare childhood eye cancer that is sometimes inherited but is most often sporadic. He observed that children who had inherited retinoblastoma often had the cancer at birth, and were at high risk of developing multiple cancers in both eyes. Children with later onset retinoblastoma usually had no family history and developed isolated tumors. Knudson reasoned that children with inherited retinoblastoma had a germline mutation in one allele of a recessive cancer gene. The germline mutation was the first of two hits in knocking out a recessive cancer gene. This is known as Knudson's two hit hypothesis. Later genetic studies found the first hit in children with inherited retinoblastoma to be a partial deletion of the long arm of chromosome 13 causing loss of the tumor suppressor gene, RB1.

These two directions of study independently identified two different classes of cancer gene, the oncogene and tumor suppressor gene, that when mutated in a given cell can set in train the sequence of events leading to the development of a cancer.

The genetics of cancer

Cancer, by definition, is a disease of the genes. Cancer is also our most common genetic disease, but only rarely is it inherited. A gene is a small part of DNA, which is the master molecule of the cell. Genes make "proteins," which are the ultimate workhorses of the cells. It is these proteins that allow our bodies to carry out all the many processes that permit us to breathe, think, move, etc.

Throughout people's lives, the cells in their bodies are growing, dividing, and replacing themselves. Many genes produce proteins that are involved in controlling the processes of cell growth and division. An alteration (mutation) to the DNA molecule can disrupt the genes and produce faulty proteins. This causes the cell to become abnormal and lose its restraints on growth. The abnormal cell begins to divide uncontrollably and eventually forms a new growth known as a "tumor" or neoplasm (medical term for cancer meaning "new growth").

In a healthy individual, the immune system can recognize the neoplastic cells and destroy them before they get a chance to divide. However, some mutant cells may escape immune detection and survive to become tumors or cancers.

Tumors are of two types, benign or malignant. A benign tumor is slow growing, does not spread or invade surrounding tissue, and once it is removed, it doesn't usually recur. A malignant tumor, on the other hand, invades surrounding tissue and spreads to other parts of the body. The hallmark of a malignant cancer is the uncontrolled clonal proliferation and spread of abnormal cancer cells. If the cancer cells have spread to the surrounding tissues, then, even after the malignant tumor is removed, it generally recurs.

A majority of cancers are caused by changes in the cell's DNA because of damage due to the environment. Environmental factors that are responsible for causing the initial mutation in the DNA are called carcinogens, and there are many types.

There are some cancers that have a genetic basis. In other words, an individual could inherit faulty DNA from his parents, which could predispose him to getting cancer. While there is scientific evidence that both factors (environmental and genetic) play a role, less than 10% of all cancers are purely hereditary. Cancers that are known to have a hereditary link are breast cancer, colon cancer, ovarian cancer, and uterine cancer. Besides genes, certain physiological traits could be inherited and could contribute to cancers. For example, inheriting fair skin makes a person more likely to develop skin cancer, but only if they also have prolonged exposure to intensive sunlight.

Most cancers are sporadic and arise in a particular tissue such as the colon, breast, lung, or skin when normal cells acquire mutations in one or more oncogenes or tumor suppressor genes. The acquisition of multiple new genetic changes is what sets the cancer cell apart from the normal cells in its surrounding tissues.

The cancer cell develops when a normal cell in an organ or tissue acquires the capacity to divide in an uncontrolled fashion. Over time the developing cancer cell starts to multiply in a clonal fashion, begins to appear different (anaplastic or undifferentiated), and progressively acquires other characteristics, such as the capacity metastasise while losing cell-to-cell adhesion. The continued acquisition of new biologic characteristics is the key to many aggressive cancers evading the host defenses, and to the resisting some treatments such chemotherapy and radiotherapy.

It is important to appreciate that oncogenes and tumor suppressor genes are in fact normal cellular genes with vital functions within normal cells. It is only when they are mutated in some way that these genes become cancer causing.

The Ha-ras gene is a good example of an oncogene. Located on chromosome 11 at the normal cellular Ha-ras gene is one of a family of ras genes and encodes a small protein that is involved in intracellular signaling. Mutations in the ras oncogenes disrupt processing of cell signals and contribute to cell transformation. Mutations in ras oncogenes are found in approximately 10% of cancers especially cancer of the colon and lung.

The most important tumor suppressor gene is the p53 gene. This gene which is known as the guardian of the genome encodes for a protein with multiple intracellular functions related to the detection of DNA damage. When DNA is damaged by exposure to a mutagen such as UV irradiation the p53 gene is expressed. The p53 protein causes the cell to stop dividing so DNA mismatch repair genes can repair the DNA. If the DNA is successfully repaired, the cell resumes normal cell functions and the p53 gene is down regulated. However, if the DNA damage is beyond repair the p53 protein switches on a process called apoptosis (programmed cell death ) leading to the death of the cell. For example, sunburn to the skin causes UV induced DNA damage, which often cannot be repaired. Expression of the p53 gene induces apoptosis the skin cells die and peel off.

Mutations in the p53 gene occur in approximately 50% of all cancers—particularly cancer of the breast, colon, lung, and brain . The mutant p53 protein is unable to stop uncontrolled cell division or switch on apoptosis, and can no longer protect the cell from acquiring additional mutation in other genes. The result is an unstable cell genome liable to further progressive DNA damage. The inherited cancer condition, Li-Fraumeni syndrome , is an autosomal dominant disorder caused by inherited mutations in the p53 gene. Individuals affected with Li-Fraumeni syndrome may develop breast cancer, brain tumors, leukemia, prostate cancer and various sarcomas at a young age.

Mismatch repair genes are another class of cancer gene contributing to instability of the cancer cell genome. Damaged DNA is repaired by an active DNA mismatch repair mechanism that identifies damaged DNA, then cuts out and repairs the the damaged DNA bases. Mutations in these repair genes are common in cancer cancers of the colon.

Oncogenes, tumor suppressor genes and other cancer causing genes can become mutated in any number of different ways. Most oncogenes become activated by specific mutations within their DNA sequence that causes the gene protein to function abnormally. Some oncogenes such MYCN are activated by DNA amplification. Oncogene amplification occurs commonly in neuroblastoma an aggressive cancer in children. These tumors can acquire hundreds of copies of this gene by DNA amplification making the cancer very resistant to treatment. Another means of oncogene activation is by its translocation from one chromosome to another. In the Burkitt lymphoma the c-myc oncogene is translocated from chromosome 8 to chromosome 14 where it becomes activated by an immunoglobulin gene. Only one allele of an oncogenes need to be activated for it to participate in cell transformation.

Tumor suppressor genes on the other hand are recessive and normally act to suppress cell replication. Cell transformation occurs when both gene alleles are inactivated (knocked out). Most commonly, inactivation of one gene allele occurs by a chromosome deletion. The second event may be an inactivating gene mutation , a second deletion or methylation of the genes promoter.

Regardless of the actual mutations involved a crucial concept in the development of most cancer is that more than one gene is usually involved in the process. Indeed in the development of cancer of the colon at least six or more separate oncogenes and tumor suppressor genes are involved in a progressive multi-step process to transform a normal colon cell into an aggressive, self replicating and invading cancer.

More recently, the application of gene expression arrays (microarrays) to the study of cancer has found that in addition to multiple gene mutations, the expression of many hundreds of non-mutant genes is affected in the process of cell transformation.

Microarray analysis of cancers of the breast and soft tissues has also identified distinctive patterns of gene expression which can be used to aid diagnosis and predict the clinical behavior of individual tumors.

This type of genetic analysis will also aid the development of new cancer therapies directed specifically at the molecular biology of the cancer.

Types of cancers

There are several different types of cancers:

• Carcinomas are cancers that arise in the epithelium (the layers of cells covering the body's surface and lining the internal organs and various glands ). Ninety percent of human cancers fall into this category. Carcinomas can be subdivided into two subtypes: adenocarcinomas and squamous cell carcinomas. Adenocarcinomas are cancers that develop in an organ or a gland, while squamous cell carcinomas refer to cancers that originate in the skin.
• Melanomas also originate in the skin, usually in the pigment cells (melanocytes).
• Sarcomas are cancers of the supporting tissues of the body, such as bone, muscle and blood vessels.
• Cancers of the blood and lymph glands are called leukemia and lymphomas respectively.
• Gliomas are cancers of the nerve tissue.

Causes and symptoms

The major risk factors for cancer are: tobacco, alcohol , diet, sexual and reproductive behavior, infectious agents, family history, occupation, environment and pollution .

According to the estimates of the American Cancer Society (ACS), approximately 40% of the cancer deaths in 1998 were due to tobacco and excessive alcohol use. An additional one-third of the deaths were related to diet and nutrition . Many of the one million skin cancers that are expected to be diagnosed each year are due to overexposure to ultraviolet light from the sun's rays.

Tobacco

Eighty to ninety percent of the lung cancer cases occur in smokers. Smoking has also been shown to be a contributory factor in cancers of upper respiratory tract, esophagus, larynx, bladder, pancreas, and probably liver, stomach, and kidney as well. Recently, scientists have also shown that second-hand smoke (or passive smoking) can increase one's risk of developing cancer.

Alcohol

Excessive consumption of alcohol is a risk factor in certain cancers, such as liver cancer. Alcohol, in combination with tobacco, significantly increases the chances that an individual will develop mouth, pharynx, larynx, and esophageal cancers.

Diet

Thirty five percent of all cancers are due to dietary causes. Excessive intake of fat leading to obesity has been associated with cancers of the breast, colon, rectum, pancreas, prostate, gall bladder, ovaries, and uterus.

Sexual and reproductive behavior

The human papilloma virus, which is sexually transmitted has been shown to cause cancer of the cervix. Having too many sex partners and becoming sexually active early has been shown to increase one's chances of contracting this disease. In addition, it has also been shown that women who do not have children or have children late in life, have an increased risk for both ovarian and breast cancer.

Infectious agents

In the later decades of the twentieth century, scientists have obtained evidence to show that approximately 15% of the world's cancer deaths can be traced to viruses, bacteria , or parasites . The most common cancer-causing pathogens and the cancers associated with them are shown in table form.

Family history

Certain cancers like breast, colon, ovarian and uterine cancer, recur generation after generation in some families. A few cancers, such as the eye cancer "retinoblastoma," a type of colon cancer, and a type of breast cancer known as "early-onset breast cancer," have been shown to be linked to certain genes that can be tracked within a family. It is therefore possible that inheriting particular genes makes a person susceptible to certain cancers.

Occupational hazards

There is evidence to prove that certain occupational hazards account for 4% of all cancer deaths. For example, asbestos workers have an increased incidence of lung cancer. Similarly, a higher likelihood of getting bladder cancer is associated with dye, rubber and gas workers; skin and lung cancer with smelters, gold miners, and arsenic workers; leukemia with glue and varnish workers; liver cancer with PVC manufacturers; and lung, bone, and bone marrow cancer with radiologists and uranium miners.

Environment

Radiation is believed to cause 1-2% of all cancer deaths. Ultra-violet radiation from the sun accounts for a majority of melanoma deaths. Other sources of radiation are x rays, radon gas, and ionizing radiation from nuclear material.

Pollution

Several studies have shown that there is a well-established link between asbestos and cancer. Chlorination of water may account for a small rise in cancer risk. However, the main danger from pollution occurs when dangerous chemicals from the industries escape into the surrounding environment. It has been estimated that 1% of cancer deaths are due to air, land and water pollution .

Cancer is a progressive disease, and goes through several stages. Each stage may produce a number of symptoms. Some symptoms are produced early and may occur due to a tumor that is growing within an organ or a gland. As the tumor grows, it may press on the nearby nerves, organs and blood vessels. This causes pain and some pressure which may be the earliest warning signs of cancer.

Despite the fact that there are several hundred different types of cancers, producing very different symptoms, the ACS has established the following seven symptoms as possible warning signals of cancer:

• changes in the size, color , or shape of a wart or a mole
• a sore that does not heal
• persistent cough, hoarseness, or sore throat
• a lump or thickening in the breast or elsewhere
• unusual bleeding or discharge
• chronic indigestion or difficulty in swallowing
• any change in bowel or bladder habits.

Many other diseases, besides cancer, could produce the same symptoms. However, it is important to have these symptoms checked, as soon as possible, especially if they linger. The earlier a cancer is diagnosed and treated, the better the chance of it being cured. Many cancers such as breast cancer may not have any early symptoms. Therefore, it is important to undergo routine screening tests such as breast self-exams and mammograms.

Diagnosis

Diagnosis begins with a thorough physical examination and a complete medical history. The doctor will observe, feel, and palpate (apply pressure by touch ) different parts of the body in order to identify any variations from the normal size, feel and texture of the organ or tissue.

As part of the physical exam, the doctor will inspect the oral cavity or the mouth. By focusing a light into the mouth, he will look for abnormalities in color, moisture, surface texture, or presence of any thickening or sore in the lips, tongue, gums, the hard palate on the roof of the mouth, and the throat. To detect thyroid cancer, the doctor will observe the front of the neck for swelling. He may gently manipulate the neck and palpate the front and side surfaces of the thyroid gland (located at the base of the neck) to detect any nodules or tenderness. As part of the physical examination, the doctor will also palpate the lymph nodes in the neck, under the arms and in the groin. Many illnesses and cancers cause a swelling of the lymph nodes.

The doctor may conduct a thorough examination of the skin to look for sores that have been present for more than three weeks and that bleed, ooze, or crust; irritated patches that may itch or hurt, and any change in the size of a wart or a mole.

Examination of the female pelvis is used to detect cancers of the ovaries, uterus, cervix, and vagina. In the visual examination, the doctor looks for abnormal discharges or the presence of sores. Then, using gloved hands the physician palpates the internal pelvic organs such as the uterus and ovaries to detect any abnormal masses. Breast examination includes visual observation where the doctor looks for any discharge, unevenness, discoloration, or scaling. The doctor palpates both breasts to feel for masses or lumps.

For males, inspection of the rectum and the prostate is also included in the physical examination. The doctor inserts a gloved finger into the rectum and rotates it slowly to feel for any growths, tumors, or other abnormalities. The doctor also conducts an examination of the testis, where the doctor observes the genital area and looks for swelling or other abnormalities. The testicles are palpated to identify any lumps, thickening or differences in the size, weight, and firmness.

If the doctor detects an abnormality on physical examination, or the patient has some symptom that could be indicative of cancer, the doctor may order diagnostic tests.

Laboratory studies of sputum (sputum cytology ), blood, urine, and stool can detect abnormalities that may indicate cancer. Sputum cytology is a test where the phlegm that is coughed up from the lungs is microscopically examined. It is often used to detect lung cancer. A blood test for cancer is easy to perform, usually inexpensive and risk-free. The blood sample is obtained by a lab technician or a doctor, by inserting a needle into a vein and is relatively painless. Blood tests can be either specific or non-specific. Often times, in certain cancers, the cancer cells release particular proteins (called tumor markers) and blood tests can be used to detect the presence of these tumor markers. However, with a few exceptions, tumor markers are not used for routine screening of cancers, because several non-cancerous conditions also produce positive results. Blood tests are generally more useful in monitoring the effectiveness of the treatment, or in following the course of the disease and detecting recurrent disease.

Imaging tests such as computed tomography scans (CT scans), magnetic resonance imaging (MRI) , ultrasound, and fiberoptic scope examinations help the doctors determine the location of the tumor even if it is deep within the body. Conventional x rays are often used for initial evaluation, because they are relatively cheap, painless and easily accessible. In order to increase the information obtained from a conventional x ray, air or a dye (such as barium or iodine) may be used as a contrast medium to outline or highlight parts of the body.

The most definitive diagnostic test is the biopsy, wherein a piece of tissue is surgically removed for microscope examination. Besides, confirming a cancer, the biopsy also provides information about the type of cancer, the stage it has reached, the aggressiveness of the cancer and the extent of its spread. Since a biopsy provides the most accurate analysis, it is considered the gold standard of diagnostic tests.

Screening examinations, conducted regularly by healthcare professionals can result in the detection of cancers of the breast, colon, rectum, cervix, prostate, testis, tongue, mouth, and skin at early stages, when treatment is more likely to be successful. Some of the routine screening tests recommended by the ACS are sigmoidoscopy (for colorectal cancer), mammography (for breast cancer), pap smear (for cervical cancer), and the PSA test (for prostate cancer). Self-examinations for cancers of the breast, testes, mouth, and skin can also help in detecting the tumors before the symptoms become serious.

A recent revolution in molecular biology and cancer genetics has contributed a great deal to the development of several tests designed to assess one's risk of getting cancers. These new techniques include genetic testing , where molecular probes are used to identify mutations in certain genes that have been linked to particular cancers.

Treatment

The aim of cancer treatment is to remove all or as much of the tumor as possible and to prevent the recurrence or spread of the primary tumor. While devising a treatment plan for cancer, the likelihood of curing the cancer has to be weighed against the side effects of the treatment. If the cancer is very aggressive and a cure is not possible, then the treatment should be aimed at relieving the symptoms and controlling the cancer for as long as possible.

Cancer treatment can take many different forms, and it is always tailored to the individual patient. The decision on which type of treatment is the most appropriate depends on the type and location of cancer, the extent to which it has already spread, the patient's age, sex, general health status and personal treatment preferences. The major types of treatment are: surgery , radiation, chemotherapy, immunotherapy, hormone therapy, and bone-marrow transplantation.

Surgery

Surgery is the removal of a visible tumor and is the most frequently used cancer treatment. It is most effective when a cancer is small and confined to one area of the body.

Surgery can be used for many purposes.

• Treatment: Treatment of cancer by surgery involves removal of the tumor to cure the disease. This is typically done when the cancer is localized to a discrete area. Along with the cancer, some part of the normal surrounding tissue is also removed to ensure that no cancer cells remain in the area. Since cancer usually spreads via the lymphatic system , adjoining lymph nodes may be examined and sometimes they are removed as well.
• Preventive surgery: Preventive or prophylactic surgery involves removal of an abnormal looking area that is likely to become malignant over time. For example, about 40% of the people with a colon disease known as ulcerative colitis, ultimately die of colon cancer. Rather than live with the fear of developing colon cancer, these people may choose to have their colons removed and reduce the risk significantly.
• Diagnostic purposes: The most definitive tool for diagnosing cancer is a biopsy. Sometimes a biopsy can be performed by inserting a needle through the skin. However, at other times, the only way to obtain some tissue sample for biopsy, is by performing a surgical operation.
• Cytoreductive surgery: is a procedure where the doctor removes as much of the cancer as possible, and then treats the remaining with radiation therapy or chemotherapy or both.
• Palliative surgery: is aimed at curing the symptoms, not the cancer. Usually, in such cases, the tumor is so large or has spread so much, that removing the entire tumor is not an option. For example, a tumor in the abdomen may be so large, that it may press on and block a portion of the intestine, interfering with digestion and causing pain and vomiting. "Debulking surgery" may remove a part of the blockage and relieve the symptoms. In tumors that are dependent on hormones , removal of the organs that secrete the hormones is an option. For example, in prostate cancer, the release of testosterone by the testicles stimulates the growth of cancerous cells. Hence, a man may undergo an "orchiectomy" (removal of testicles) to slow the progress of the disease. Similarly, in a type of aggressive breast cancer, removal of the ovaries (oophorectomy) will stop the synthesis of hormones from the ovaries and slow the progression of the cancer.

Radiation

Radiation kills cells. Radiation is used alone in cases where a tumor is unsuitable for surgery. More often, it is used in conjunction with surgery and chemotherapy. Radiation can be either external or internal. In the external form, the radiation is aimed at the tumor from outside the body. In internal radiation (also known as brachytherapy), a radioactive substance, in the form of pellets or liquid is placed at the cancerous site by means of a pill, injection, or insertion in a sealed container.

Chemotherapy

Chemotherapy is the use of drugs to more specifically kill cancer cells. It destroys the hard-to-detect cancer cells that have spread and are circulating in the body. Chemotherapeutic drugs can be taken either orally (by mouth) or intravenously, and may be given alone or in conjunction with surgery, radiation, or both.

When chemotherapy is used before surgery or radiation, it is known as primary chemotherapy or "neoadjuvant chemotherapy." An advantage of neoadjuvant chemotherapy is that since the cancer cells have not been exposed to anti-cancer drugs, they are especially vulnerable. It can therefore be used effectively to reduce the size of the tumor for surgery or target it for radiation. However, the toxic effects of neoadjuvant chemotherapy are severe. In addition, it may make the body less tolerant to the side effects of other treatments that follow such as radiation therapy. The more common use of chemotherapy is adjuvant therapy, which is given to enhance the effectiveness of other treatments For example, after surgery, adjuvant chemotherapy is given to destroy any cancerous cells that still remain in the body.

Immunotherapy

Immunotherapy uses the body's own immune system to destroy cancer cells. This form of treatment is being intensively studied in clinical trials and is not yet widely available to most cancer patients. The various immunological agents being tested include substances produced by the body (such as the interferons , interleukins, and growth factors), monoclonal antibodies, and vaccines. Unlike traditional vaccines, cancer vaccines do not prevent cancer. Instead, they are designed to treat people who already have the disease. Cancer vaccines work by boosting the body's immune system and training the immune cells to specifically destroy cancer cells.

Hormone therapy

Hormone therapy is standard treatment for some types of cancers that are hormone-dependent and grow faster in the presence of particular hormones. These include cancer of the prostate, breast, and uterus. Hormone therapy involves blocking the production or action of these hormones. As a result the growth of the tumor slows down and survival may be extended for several months or years.

Bone marrow transplantation

The bone marrow is the tissue within the bone cavities that contains blood-forming cells. Healthy bone marrow tissue constantly replenishes the blood supply and is essential to life. Sometimes, the amount of drugs or radiation needed to destroy cancer cells also destroys bone marrow. Replacing the bone marrow with healthy cells counteracts this adverse effect. A bone marrow transplant is the removal of marrow from one person and the transplant of the blood-forming cells either to the same person or to some one else. Bone-marrow transplantation, while not a therapy in itself, is often used to "res cue" a patient, by allowing those with cancer to undergo very aggressive therapy.

Many different specialists generally work together as a team to treat cancer patients. An oncologist is a physician who specializes in cancer care. The oncologist provides chemotherapy, hormone therapy, and any other non-surgical treatment that does not involve radiation. The oncologist often serves as the primary physician and co-ordinates the patient's treatment plan.

The radiation oncologist specializes in using radiation to treat cancer, while the surgical oncologist performs the operations needed to diagnose or treat cancer. Gynecologist-oncologists and pediatric-oncologists, as their titles suggest, are physicians involved with treating women's and children's cancers respectively. Many other specialists may also be involved in the care of a cancer patient. For example, radiologists specialize in the use of x rays, ultrasounds, computed tomography scans (CT scans), MRI imaging, and other techniques that are used to diagnose cancer. Hematologists specialize in disorders of the blood and are consulted in case of blood cancers and bone marrow cancers. The samples that are removed for biopsy are sent to a laboratory, where a pathologist examines them to determine the type of cancer and extent of the disease. Only some of the specialists who are involved with cancer care have been mentioned above. There are many other specialties, and virtually any type of medical or surgical specialist may become involved with care of the cancer patient should it become necessary.

Alternative treatment

There are a multitude of alternative treatments available to help the person with cancer. They can be used in conjunction with, or separate from, surgery, chemotherapy, and radiation therapy. Alternative treatment of cancer is a complicated arena and a trained health practitioner should be consulted.

The effectiveness of complementary therapies such as acupuncture in alleviating cancer pain has not been clinically proven. Bodywork therapies such as massage and reflexology ease muscle tension and may alleviate the side effects such as nausea and vomiting. Homeopathy and herbal remedies used in Chinese traditional herbal medicine have also been reported to alleviate some of the side effects of radiation and chemotherapy and are being recommended by many doctors.

Certain foods including many vegetables , fruits , and grains are believed to offer protection against various cancers. However, isolation of the individual constituent of vegetables and fruits that are anti-cancer agents has proven difficult. In laboratory studies, vitamins such as A, C and E, as well as compounds such as isothiocyanates and dithiolthiones found in broccoli, cauliflower, and cabbage, and beta-carotene found in carrots have been shown to protect against cancer. Studies have shown that eating a diet rich in fiber as found in fruits and vegetables reduces the risk of colon cancer. Exercise and a low fat diet help control weight and reduce the risk of endometrial, breast, and colon cancer.

Certain drugs, which are currently being used for treatment, could also be suitable for prevention. For example, the drug tamoxifen (Nolvadex), that has been very effective against breast cancer, is currently being tested by the National Cancer Institute, for its ability to prevent cancer. Similarly, retinoids derived from vitamin A are being tested for their ability to slow the progression or prevent head and neck cancers. Certain studies have suggested that cancer incidence is lower in areas where soil and foods are rich in the mineral selenium. More trials are needed to explain these intriguing connections.

Prognosis

"Life-time risk" is the term that cancer researchers use to refer to the probability that an individual, over the course of a lifetime will develop cancer or die from it. In the United States, men have a one in two lifetime risk of developing cancer, and for women the risk is one in three. Overall, African-Americans are more likely to develop cancer than whites. African-Americans are also 30% more likely to die of cancer than whites.

Most cancers are curable if detected and treated at their early stages. A cancer patient's prognosis is affected by many factors, particularly the type of cancer the patient has, the stage of the cancer, the extent to which it has metastasized and the aggressiveness of the cancer. In addition, the patient's age, general health status, and the effectiveness of the treatment being pursued are also important factors.

To help predict the future course and outcome of the disease and the likelihood of recovery from the disease, doctors often use statistics . The five-year survival rates are the most common measures used. The number refers to the proportion of people with cancer who are expected to be alive, five years after initial diagnosis, compared with a similar population that is free of cancer. It is important to note that while statistics can give some information about the average survival experience of cancer patients in a given population, it cannot be used to indicate individual prognosis, because no two patients are exactly alike.

Prevention

According to nutritionists and epidemiologists from leading universities in the United States, a person can reduce the chances of getting cancer by following some simple guidelines:

• Eating plenty of vegetables and fruits
• Exercising regularly
• Avoiding excessive weight gain
• Avoiding tobacco (including second hand smoke)
• Avoiding excessive amounts of alcohol
• Avoiding the midday sun (between 11 a.m. and 3 p.m.) when the suns rays are the strongest
• Avoiding risky sexual practices
• Avoiding known carcinogens in the environment or work place.

See also Gene therapy; Immunology; Nuclear medicine; Radioisotopes in medicine; Stem cells.

Resources

books

Haskell, Charles M. Cancer Treatment. 5th. ed. Philadelphia: W.B. Saunders, 2001.

Rosenbaum, Ernst H. MD, et al. Everyone's Guide to Cancer Therapy. 4th. ed. Andrews McMeel Publishing, 2002.

Steingraber, Sandra. Living Downstream: A Scientist's Personal Investigation of Cancer and the Environment. Vintage Books, 1998.

periodicals

Brookes, Anthony, "Rethinking Genetic Strategies to Study Complex Diseases," Trends in Molecular Medicine (November 2001): 512–6.

other

National Institutes of Health. "National Cancer Institute." (February 5, 2003).<http://www.nci.nih.gov/>.

Lata Cherath

Micheal Sullivan

KEY TERMS

Benign

—A growth that does not spread to other parts of the body. Recovery is favorable with treatment.

Biopsy

—The surgical removal of a small part of a tumor. The excised tissue is studied under the microscope to determine whether it is benign or malignant.

Bone marrow

—A spongy tissue located in the hollow centers of certain bones, such as the skull and hip bones. Bone marrow is the site of blood cell generation.

Carcinogen

—Any substance capable of causing cancer by mutating the cell's DNA.

Chemotherapy

—Use of powerful drugs to kill cancer cells in the human body.

Epithelium

—The layer of cells that covers external and internal surfaces of the body. The many types of epithelium range from flat cells to long cells to cubed cells.

Hormone therapy

—Treatment of cancer by inhibiting the production of hormones, such as testosterone and estrogen.

Immunotherapy

—Treatment of cancer by stimulating the body s immune defense system.

Malignant

—A general term for cells that can dislodge from the original tumor, invade and destroy other tissues and organs.

Metastasis

—The spread of cancer from one part of the body to another.

Radiation therapy

—Treatment using high-energy radiation from x-ray machines, cobalt, radium, or other sources.

Sore

—An open wound or a bruise or lesion on the skin.

Tumor

—An uncontrolled growth of tissue, either benign (noncancerous) or malignant (cancerous).

X ray

—Electromagnetic radiation of very short wavelength, and very high energy.

Cancer

Definition

Cancer is characterized by uncontrolled growth of cells in the body and the ability of these malignant cells to spread (metastasize) to distant sites within the body. If the spread is not controlled, cancer can result in death. Cancer is not just one disease but a group of almost one hundred different types of malignant diseases.

Description

Cancer, by definition, is a disease of the genes. A gene is a small part of DNA, which is the instruction manual of the cell. Genes hold the instructions to make proteins , which carry out many of the body's functions. It is these proteins that allow the human body to carry out all the processes that permit people to breathe, think, move, etc.

Throughout people's lives the cells in their bodies grow, divide, and replace themselves. Many genes produce proteins that are involved in controlling the processes of cell growth and division. An alteration (mutation) to the DNA molecule can disrupt some of the genes on the DNA molecule and produce faulty proteins. This causes a cell to loose restraint on growth. The abnormal cell begins to divide uncontrollably and eventually forms a new growth known as a tumor or neoplasm (medical terms for cancer meaning new growth). In a healthy body the immune system can recognize neoplastic (abnormal) cells and destroy them before they get a chance to divide. Even so, some mutant cells may escape immune detection and survive to develop into cancerous growths.

Tumors are divided into two general categories: benign or malignant. A benign tumor is slow growing and does not spread or invade surrounding tissue. Once it is removed it doesn't usually recur. A malignant tumor, on the other hand, invades surrounding tissue and can spread to other parts of the body. Malignant tumors can be removed; however, if the cancer cells have spread to the surrounding tissues, the tumor is likely to recur.

A majority of cancers are caused by changes in the cell's DNA that are due to the environment. Environ- mental factors that are responsible for causing the initial mutation in the DNA are called carcinogens. Internal factors can cause cancer as well. Certain hormones have been shown to have an effect the growth or control of a particular cell line. Hormones are substances made by one organ and passed through the bloodstream to perform a function in another organ.

While there is scientific evidence that both environ- mental and genetic factors play a role in most cancers, approximately 5–10% of all cancers are classified as hereditary (genetic). This means a faulty gene that leads to a cancer is passed from parent to child. This poses a greater risk for that particular type of cancer in certain descendants of the family. However, having a cancer- causing gene does not necessarily mean that person will automatically get cancer. Rather, it means that person is predisposed to a type of cancer, or more likely to get this cancer when compared to the general population. Cancers known to have a hereditary tendency in some cases include breast cancer , colon cancer, ovarian cancer, skin cancer, and prostate cancer .

Aside from genes, certain inherited physiological traits can contribute to cancers. For example, inheriting fair skin makes a person more likely to develop skin cancer, but only if they also have prolonged exposure to intensive sunlight.

There are many different types of cancers. Some of the most common types include:

• Carcinomas. These cancers arise in the epithelium (layers of cells in the skin covering the body's surface and lining the internal organs and various glands). About 80% of human cancers fall into this category. Carcinomas can be subdivided into two subtypes: adenocarcinomas, which are cancers that develop in an organ or a gland; and squamous cell carcinomas, cancers that originate in the skin.
• Melanomas. This form also originates in the skin, usually in the pigment cells (melanocytes), and can quick- ly metastasize to internal organs.
• Sarcomas. Cancers of the supporting tissues of the body, such as bone, muscle, cartilage, and fat.
• Leukemias. Cancers of the blood or blood-forming organs.
• Lymphomas. Cancer of the lymphatic system , the network of vessels and nodes that acts as a filtration system, distributing nutrients to blood and tissue and preventing bacteria and other foreign substances from entering the bloodstream.
• Gliomas. Cancers of nerve tissue.

The most common cancers are skin cancer, lung cancer , colon and rectal (colorectal) cancer, breast cancer (in women), and prostate cancer (in men). In addition, cancer of the kidneys , ovaries, uterus, pancreas , bladder, and blood and lymph-node cancer (leukemias and lymphomas) are also included among the 12 major cancers that affect most Americans.

Almost every tissue can give rise to cells that cause cancer and each of these cancers is very different in its symptoms and prognosis. However, there are basic and similar genetic processes that lead to tumor growth in the human body. Genes are responsible for producing proteins that regulate cell growth and division. When these genes do not function properly, the proteins are abnormal and cells can grow uncontrollably. This results in the formation of a tumor. As more genetic mutations (changes) occur in this tumor, it becomes more life-threatening and has a greater chance of spreading to other parts of the body.

Three classes of genes appear to play a role in the development of cancer:

• Proto-oncogenes encourage and promote the normal growth and division of cells. When they are defective, they become oncogenes. Oncogenes are overactive proto-oncogenes that cause excessive cell multiplication that can lead to tumors.
• Tumor suppressor genes act as brakes on cell growth. They prevent cells from multiplying uncontrollably. If these genes are defective there is no control over cell growth and tumors can result.
• DNA repair genes ensure that each strand of DNA is correctly copied during cell division . When these genes do not function properly, the replicated DNA is likely to have errors. This causes defects in other genes and can lead to tumor formation in some cases.

Approximately 5–10% of cancers have a hereditary component. In these cancers a child does not inherit caner

from the parents. Rather, a predisposition to cancer is inherited. For example, a faulty tumor suppressor gene may be inherited. This gene is not able to control cell growth but the corresponding gene inherited from the other parent is still functional. Cell growth is under control. However, as a child grows up, radiation, pollution, or any other environmental factor could change the functional gene, making it defective as well. Now, neither of these tumor suppressor genes are functioning, and it is likely that a tumor will develop. Defects in proto-oncogenes and DNA repair genes can be inherited, as well, leaving a person more vulnerable to cancer than the general population.

Some cancers seem to run in families. In these cancers there is no specific gene responsible for the clustering of cancer in a family. However, a particular type of cancer may be seen more often than in the general population. It is suggested that this is due to a combination of genetic and environmental factors.

Cancer kills one out of every four Americans. As of 2001 it was the second leading cause of death in the United States, surpassed only by heart disease. More than 1.2 million new cases of cancer are diagnosed every year in the United States. The National Cancer Institute estimates that approximately 8.4 million Americans alive in 2001 had a history of cancer. Some of these people were cured while others were still affected with the dis- ease and possibly undergoing treatment.

Anyone is at risk for developing cancer. Since the occurrence of cancer increases as a person ages, most cases are seen in adults middle-aged or older. Nearly 80% of cancers are diagnosed in people 55 years of age and older.

Lifetime risk is the term used to refer to the probability that an individual will develop cancer over the course of his or her lifetime. In the United States men have a one-in-two lifetime risk of developing cancer. For women, the risk is one in three. Overall, African Americans are more likely to develop cancer than Caucasians and are 33% more likely to die of cancer than Caucasians.

The major risk factors for cancer are tobacco, alcohol, diet, sexual and reproductive behavior, infectious agents, family history, occupation, environment, and pollution.

Tobacco

Eighty-to-ninety percent of lung cancer cases occur in smokers. Smoking has also been shown to be a contributory factor in cancers of mouth, pharynx, larynx, esophagus, pancreas, uterine cervix, kidney, and bladder. Smoking accounts for at least 30% of all cancer deaths. Scientists have shown that inhaling secondhand smoke (passive smoking) can increase one's risk of developing cancer.

Alcohol

Excessive consumption of alcohol is a risk factor in certain cancers such as liver and breast cancer. Alcohol, in combination with tobacco, significantly increases the chances that an individual will develop mouth, pharynx, larynx, and esophageal cancers. The combined effect of tobacco and alcohol is greater than the sum of their individual effects. This is called synergy.

Diet and physical activity

One-third of all cancer deaths are due to a poor adult diet. High-fat diets have been associated with cancers of the colon and rectum, prostate, endometrium, and possibly breast. Consumption of meat, especially red meat, has been associated with increased cancer at various sites such as the colon and prostate. Additionally, a high-calorie diet and low level of physical activity can lead to obesity , which increases the risk for cancer at various sites including the breast, colon and rectum, prostate, kidney, and endometrium.

Sexual and reproductive behavior

The human papilloma virus, a sexually transmitted disease, has been shown to cause cancer of the cervix. Having many sexual partners and becoming sexually active early has been shown to increase one's chances of contracting this disease and, therefore, developing cervical cancer. In addition, it has also been shown that women who do not have children or those who have children late in life have an increased risk for both ovarian and breast cancer.

Hormone replacement therapy

As women go through menopause , a physician may recommend hormone replacement therapy. This involves taking female hormones (called estrogen and progesterone) to control certain symptoms such as hot flashes and vaginal dryness that occur during this time of a woman's life. Taking estrogen alone can increase the risk for uterine cancer. However, progesterone is often prescribed at the same time to counteract the cancerous effects of estrogen. There is a questionable relationship between hormone replacement therapy and breast cancer as well. As of 2001, this relationship was not fullyunderstood.

Family history

Certain cancers tend to occur more commonly among members of a family. Much of the time this seems to happens by chance, or is due to a common family habit such as cigarette smoking or extended sun exposure. However, certain cancers can occur in excess in some families due to a genetic predisposition that is passed from generation to generation. For example, if the BRCA1 gene is defective in a family, members of that family may have an increased risk to develop breast, colon, ovarian, or prostate cancer. Other defective genes can make persons susceptible to other types of cancer. Therefore, inheriting particular genes can increase a person's chance of developing cancer.

Occupational hazards

There is ample evidence that occupational hazards account for 4% of all cancer deaths. For example, asbestos workers have an increased incidence of lung cancer. Similarly, bladder cancer is associated with dye, rubber, and gas workers; skin and lung cancer with people who are smelters, gold miners and arsenic workers; leukemia is seen more frequently in people who work with glue and varnish; liver cancer is more prevalent in PVC manufacturers; and lung, bone, and bone marrow cancer is associated with radiologists and uranium miners.

Environment

High-frequency radiation has been shown to cause human cancer. Ultraviolet radiation from the sun accounts for a majority of melanoma cases. Other sources of radiation are x rays, radioactive substances, and rays that enter the earth's atmosphere from outer space. Virtually any part of the body can be affected by these types of radiation, especially bone marrow and the thyroid gland .

Additionally, being exposed to substances such as certain chemicals, metals, or pesticides, can increase the risk of cancer. Asbestos is an example of a well-known carcinogen, increasing the risk for lung cancer. This risk is increased even further for a smoker who is exposed to asbestos over a period of time.

Causes and symptoms

Cancer is a progressive disease and goes through several stages. Each stage can produce a number of symptoms. Unfortunately, many types of cancer do not display any obvious symptoms or cause pain until the disease has progressed to an advanced stage. Early signs of cancer are often subtle and are easily mistaken for signs of other less-dangerous diseases.

Despite the fact that there are several hundred different types of cancers producing very different symptoms, the American Cancer Society (ACS) has established the following seven symptoms as possible warning signals of cancer:

• changes in the size, color, or shape of a wart or a mole
• a sore that does not heal
• persistent cough, hoarseness, or sore throat
• a lump or thickening in the breast or elsewhere
• unusual bleeding or discharge
• chronic indigestion or difficulty in swallowing
• any change in bowel or bladder habits

Other diseases can produce similar symptoms. However, it is important to have these symptoms checked as soon as possible, especially if they linger. The earlier a cancer is diagnosed and treated, the better the chance of it being cured. Many cancers, for example breast cancer, may not have any early symptoms. Therefore, it is important to undergo routine screening tests, such as breast self-exams and mammograms.

Diagnosis

If a person has symptoms of cancer, a physician will begin with a complete medical history and a thorough physical examination . The doctor will examine different parts of the body in order to identify any variations from the normal size, feel, and texture of the organ or tissue. In addition to the physical exam, the doctor may order various tests.

Laboratory tests on blood and urine are often used to obtain information about a person's health. If cancer is suspected, a special test can be done that measures the amount of certain substances, called tumor markers, in the blood, urine, or particular tissues. These proteins are released from some types of cancer cells. Thus, the levels of these substances may be abnormal when certain cancers are present. However, laboratory tests alone cannot be used to make a definitive diagnosis of cancer. Blood tests are generally more useful in monitoring the effectiveness of the treatment or in following the course of the disease and detecting any signs of recurrence.

A doctor may look for tumors by examining images of areas inside the body. The most common way to obtain these images is by using x rays. Other techniques used to examine the insides of the body include computed tomography (CT scan), magnetic resonance imaging (MRI), and ultrasonography.

The most definitive diagnostic test is a biopsy. In this technique a piece of tissue is surgically removed for examination under a microscope . A biopsy provides information about the cellular nature of an abnormality: the stage it has reached, the aggressiveness of the cancer, and the extent of its spread. Further analysis of the tissue obtained by biopsy defines the cause of the abnormality. Since a biopsy provides the most accurate analysis, it is considered the gold standard of diagnostic tests for cancer.

Regular screening examinations conducted by healthcare professionals can result in the early detection of various types of cancer. Early detection means treatment is more likely to succeed. For example, the ACS recommends an annual mammogram (x ray of the breast) for women over the age of 40 years, to screen for breast cancer. It also recommends a sigmoidoscopy , in which a thin, lighted tube with a tiny camera is used to view the inside of the colon, every five years for people over the age of 50. This technique can assess the presence of colorectal cancer . Self-examinations for cancers of the breast, testes, mouth, and skin can also help in detecting tumors before the symptoms become serious.

Evolutions in molecular biology and the genetics of cancer have led to the development of several tests designed to assess one's risk of getting certain types of cancer. Genetic testing involves looking closely at certain genes that have been linked to particular cancers. As of 2001 there were many limitations to genetic testing. Tests could be uninformative and to a very small proportion of individuals tested. Additionally, concerns exist about insurance coverage and employment discrimination for someone who has an increased risk for cancer. As of 2001 these tests were reserved only for very specific individuals. A hereditary cancer clinic can help assess who may benefit from this type of testing.

Treatment

The aim of cancer treatment is to remove all or as much of the tumor as possible and to prevent the recur- rence or spread of the primary tumor. While devising a treatment plan for cancer, the likelihood of curing the cancer must be weighed against the side effects of the treatment. If the cancer is aggressive and a cure is not possible, then treatment should be aimed at relieving the symptoms and controlling the cancer for as long as possible.

Cancer treatment can take many different forms, and it is always tailored to an individual. The decision on which type of treatment is the most appropriate depends upon the type and location of the cancer and the extent to which it has already spread. A physician will also consider an affected person's age, sex, general health status, and personal treatment preferences. Treatment can be local, meaning that it affects cancer cells in the tumor and the surrounding area only. Surgery and radiation are local treatments. Treatment can also be systemic, meaning that the treatment travels through the bloodstream and affects cancer and other cells throughout the entire body. Chemotherapy , immunotherapy, and hormone therapy are examples of systemic treatments.

Surgery

Surgery can be used for many purposes:

• Treatment. Treatment of cancer by surgery involves removal of the tumor to cure the disease. This is typically done when the cancer is localized to a discrete area. Along with the cancer, some of the surrounding tissue is also removed to ensure that no cancer cells remain in the area. Since cancer usually spreads via the lymphatic system, lymph nodes near the tumor site may be removed for examination.
• Prevention. Preventive or prophylactic surgery involves removal of an abnormal-looking area that is likely to become malignant over time. For example, 40% of people with a colon disease called ulcerative colitis ultimately die of colon cancer. Rather than live with the fear of developing colon cancer, these people may choose to have their colons removed in order to reduce their risk of colorectal cancer.
• Diagnosis. The most definitive tool for diagnosing cancer is a biopsy. Sometimes a biopsy can be performed by inserting a needle through the skin and aspirating a small amount of fluid or tissue. At other times the only way to obtain a tissue sample is through surgery.
• Cytoreductive surgery. This is a surgical procedure in which the surgeon removes as much of the cancer as possible. The remaining cancer cells are then treated with radiation therapy, chemotherapy, or both.
• Palliative surgery. This type of surgery is intended to relieve cancer symptoms or slow the progression of disease. It is not designed to cure the cancer. For example, if the tumor is very large or has spread to many places in the body, removing the entire tumor may not be an option. However, by decreasing the size of the tumor, pain may be alleviated. This is known as debulking surgery.

Radiation therapy

Radiation uses high-energy rays to kill cancer cells. This technique may be used instead of surgery. It also may be utilized before surgery to shrink a tumor or after surgery to destroy any remaining cancer cells.

Radiation can be either external or internal. In the external form, the radiation comes from a machine that aims the rays at the tumor. In internal radiation (also known as brachytherapy), radioactive material is sealed in needles, seeds, or wires and placed directly in or near the tumor. Radiation may lead to various side effects, such as fatigue, hair loss, and a susceptibility to infections. However, these side effects can usually be controlled.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. The entire body is exposed to the drugs (systemic therapy) in an effort to destroy the hard-to-detect cancer cells that have spread and are circulating in the body. The cancer cells are affected more dramatically than normal cells because they are rapidly dividing. Chemotherapeutic drugs can be injected into a vein, the muscle, or the skin, or they may be taken by mouth.

When chemotherapy is used before surgery, it is known as primary, or neoadjuvant chemotherapy. Its purpose is usually to reduce the size of the tumor. The more common use of chemotherapy is in adjuvant therapy. In this technique, chemotherapy is given after surgery to destroy any remaining cancer cells and to help prevent cancer from recurring. Chemotherapy can also be used in conjunction with radiation.

Side effects of chemotherapy vary but can include susceptibility to infections, fatigue, poor appetite, weight loss, nausea, diarrhea , and hair loss. Decreased fertility can be a long-term side effect in some instances.

Bone marrow failure is a complication of chemotherapy. When high-dose chemotherapy is utilized, bone

marrow failure is anticipated. Bone marrow transplantation (BMT) or peripheral stem cell transplantation (PSCT) are techniques used to treat this complication. Both techniques provide healthy stem cells for an affected person. Stem cells are immature cells that mature into blood cells. Transplanted stem cells replace the patient's stem cells that have been damaged or destroyed by chemotherapy or radiation. This procedure allows an individual to undergo very aggressive treatment for cancer. Those who receive BMT or PSCT have an increased risk of infection , bleeding, and other side effects due to the chemotherapy and radiation. Graft-versus-host dis- ease may also occur. This complication develops when the donated marrow reacts against the recipient's tissues. It can occur any time after the transplant. Drugs may be given to reduce the risk of graft-versus-host disease and to treat the problem if it occurs.

Immunotherapy

Immunotherapy, also called biological therapy, is the use of treatments that promote or support the body's immune system response to cancer. The side effects of immunotherapy are variable but include flu- like symptoms, weakness, loss of appetite, and skin rash. These symptoms will subside after the treatment is completed.

Hormone therapy

Hormone therapy is used to fight certain cancers that depend on hormones for their growth. Drugs can be used to block the production of hormones or change the way they work. Additionally, organs that produce hormones may be removed. As a result of this therapy, the growth of the tumor slows and survival may be extended for several months or years.

Alternative and complementary therapies

There are certain cancer therapies that have not been scientifically tested and approved. If these unproven treatments are used instead of the standard therapy, this is known as alternative therapy. If they are used along with standard therapy, this is known as complementary therapy. Alternative therapy is considered dangerous because some of these unproven treatments might have life- threatening side effects. Additionally, persons who use alternative therapy may lose the opportunity to benefit from standard, proven therapy. However, some complementary therapies may help to relieve symptoms of cancer, decrease the magnitude of side effects from treatment, or improve a patient's sense of well being. The American Cancer Society recommends that anyone considering alternative or complementary therapy consult a health care team before doing so.

Palliative care

Palliative care, which focuses on the terminally ill, is an extremely important aspect of care. Its goal is to prevent and relieve pain and suffering through symptom management, and addresses not only the physical, but the practical, emotional, and spiritual needs of patients, their families, and caregivers. By viewing dying as a natural process, palliative care helps facilitate what can be termed a "good" death, free from suffering and stress . Many patients and their families are unaware that suffering at the end of life is no longer necessary. Health care professionals can relieve a patient and their loved ones of much anxiety by informing them that appropriate symptom management is readily available.

Hospice care

Hospice care is the environment in which palliative care is given to terminally ill patients. Hospice care can be provided either at home, or in a home-like facility called a hospice. Hospice care focuses on providing the best possible palliative care for the patient until the patient dies.

Prognosis

Most cancers are curable if detected and treated in their early stages. The prognosis for a person with cancer is affected by many factors, particularly the type of cancer and stage of the cancer, the extent to which it has metastasized, and its aggressiveness. In addition, a person's age, general health status, and effectiveness of the treatment being pursued are important factors.

To help predict the outcome of cancer and the likeli- hood of recovery from the disease, five-year survival rates are used. In the United States, as of 2001, the five- year survival rate for all cancers combined was 59%. This means that 59% of people with cancer are expected to be alive five years after they are diagnosed. These people may be free of cancer, or they may be undergoing treatment. It is important to note that, while this statistic can give some information about the average survival of people with cancer in a given population, it cannot be used to predict the course of cancer for an individual. No two people are exactly alike. The five-year survival rate does not account for differences in detection methods, types of treatments, additional illnesses, and personal behavior of the individual.

Health care team roles

Family physicians, internists, gynecologists, or pediatricians generally make an initial diagnosis of cancer. Other physicians, notable radiologists, and oncologists provide chemotherapeutic and radiologic treatment. Nurses provide emotional and educational support, home care , home hospice care, and case management. Counselors and psychologists may provide emotional support to patients and their families. Epidemiologists collect and maintain data related to cancer.

Prevention

According to experts from leading universities in the United States, a person can reduce the chances of getting cancer by following these guidelines:

• eating plenty of fruits and vegetables
• exercising vigorously for at least 20 minutes every day
• avoiding excessive weight gain
• avoiding tobacco (including second hand smoke)
• decreasing or avoiding consumption of animal fats and red meats
• avoiding excessive amounts of alcohol
• avoiding the midday sun (between 11 a.m. and 3 p.m.) when the sun's rays are the strongest
• avoiding risky sexual practices
• avoiding known carcinogens in the environment or work place

Certain drugs being used for treatment can also be suitable for prevention. For example, tamoxifen (Nolvadex) has been very effective against recurrence of breast cancer and is now thought to be helpful in the prevention of breast cancer. Similarly, retinoids derived from vitamin A are being tested for their ability to slow the progression of, or prevent, head and neck cancers.

KEY TERMS

Benign —A growth that does not spread to other parts of the body. Recovery is favorable with treatment.

Biopsy —The surgical removal and microscopic examination of living tissue for diagnostic purposes.

Bone marrow —Spongy material that fills the inner cavities of the bones. The progenitors of all the blood cells are produced in this bone marrow.

Carcinogen —Any substance capable of causing cancer by mutating a cell's DNA.

Chemotherapy —Treatment with anticancer drugs.

Epithelium —Layer of cells covering the body's surface and lining the internal organs and various glands.

Hormone therapy —Treatment of cancer by changing the hormonal environment, such as testosterone and estrogen.

Immunotherapy —Treatment of cancer by stimulating the body's immune system.

Malignant —A general term for cells that can break loose from an original tumor, invade, and then destroy other tissues and organs.

Metastasis —The spread of cancer from one part of the body to another.

Radiation therapy —Treatment using high-energy radiation from x-ray machines, cobalt, radium, or other sources.

Sore —An open wound or a bruise or lesion on the skin.

Tumor —An abnormal growth resulting from a cell that lost its normal growth control restraints and started multiplying uncontrollably.

X rays —High energy radiation used in high doses, either to diagnose or treat disease.

Resources

BOOKS

Armstrong-Dailey, Ann, and Sarah Zarbhock. Hospice Care for Children. New York: Oxford, 2001.

Bragg, Rubin. Oncologic Imaging. 2^nd ed. Philadelphia: Saunders, 2001.

Crist, William M, et al. "Neoplastic Diseases and Tumors." In Nelson Textbook of Pediatrics. 16^th ed. Ed. Richard E. Behrman et al., Philadelphia: Saunders, 2000, 1531-1573.

Eyre, Harmon J. Dianne Lange, and Lois B. Morris. Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment, and Recovery. Washington: American Cancer Society, 2001.

Hudson, Christopher N. Textbook of Ovarian Cancer. 2^nd ed. New York: Oxford, 2001.

Ihde, Daniel C., and Dan L. Longo. "Presentations of the Patient with Cancer." In Harrison's Principles of Internal Medicine. 14^th ed. Ed. Anthony S. Fauci, et al., New York: McGraw-Hill, 1998, 360-362.

Kantoff, Philip. Prostate Cancer: Principles and Practice. Philadelphia: Lippincott Williams & Wilkins, 2001.

Lippman, Marc E. "Evaluation of Breast Masses in Men and Women." In Harrison's Principles of Internal Medicine, 14^th ed. Ed. Anthony S. Fauci, et al., New York: McGraw-Hill, 1998, 362-365.

Longo, Dan L., et al. "Oncology." In Harrison's Principles of Internal Medicine. 14^th ed. Ed. Anthony S. Fauci, et al., New York: McGraw-Hill, 1998, 493-633.

Rosenbaum, Ernest H. Supportive Cancer Care: The Complete Guide for Patients and Families. Naperville: Sourcebooks Trade, 2001.

Simone, Joseph M., et al., "Oncology." In Cecil Textbook of Medicine 21^st ed. Ed. Lee Goldman and J. Claude Bennett, Philadelphia: W.B. Saunders, 2000, 1029-1081.

PERIODICALS

Feldt-Rasmussen U. "Iodine and Cancer." Thyroid 11, no. 5 (2001): 483-486.

Izquierdo-Porrera, A.M., J. Trelis-Navarro, X. Gomez-Batiste. "Predicting Place of Death of Elderly Cancer Patients Followed by a Palliative Care Unit." Journal of Pain Symptom Management 21, no. 6 (2001): 481-490.

Kutner J.S., C.T. Kassner, and D.E. Nowels. "Symptom Burden at the End of Life. Hospice Providers' Perceptions." Journal of Pain Symptom Management 21. no. 6 (2001): 473-480.

Messmann, H., and K. Schlottmann. "Role of Endoscopy in the Staging of Esophageal and Gastric Cancer." Seminars in Surgical Oncology 20, no.2 (2001): 78-81.

Nelson, R.L. "Iron and Colorectal Cancer Risk: Human Studies." Nutrition Review 59, no. 5 (2001): 140-148.

Skarin, A.T., R.S., Herbst, T.L. Leong, A. Bailey, and D. Sugarbaker. "Lung Cancer in Patients Under 40." Lung Cancer 32, no. 3 (2001): 255-264.

ORGANIZATIONS

American Academy of Physical Medicine and Rehabilitation. One IBM Plaza, Suite 2500, Chicago, IL 60611-3604.(312) 464-9700. <http://www.aapmr.org/consumers/public/amputations.htm>.

American College of Occupational and Environmental Medicine. 55 West Seegers Road, Arlington Heights, IL60005. (708) 228-6850. <http://www.acoem.org>.

American College of Radiology. 1891 Preston White Drive, Reston, VA 20191. (703) 648-8900.<http://www.acr.org>.

American College of Surgeons. 633 North St. Clair Street, Chicago, IL 60611-32311. (312) 202-5000. <http://www.facs.org/>.

American Lung Association. 1740 Broadway, New York, NY 10019.(212)-315-8700. <http://www.lungusa.org/diseases/lungtb.html>.

American Melanoma Foundation. 3914 Murphy Canyon Road, Suite A132, San Diego, CA 92123. (858) 277-4426. <http://www.melanomafoundation.org/homepage.html>.

National Alliance of Breast Cancer Organizations. 9 East 37^th Street, New York, NY 10016. (212) 889-0606. <http://www.nabco.org/>.

National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethjesda, MD 20892-2580.(800) 422-6237, or (301) 435-3848. <http://www.nci.nih.gov/>.

Skin Cancer Foundation. 245 5^th Avenue, Suite #1403, New York, NY 10016. (800) 754-6490. <http://www.skincancer.org/melanoma/>.

OTHER

American Cancer Society. <http://www2.cancer.org/contact/>.

Canadian Cancer Society. <http://www.cancer.ca/>.

Cancer Care. <http://www.cancercare.org/>.

Cancer Guide. <http://www.cancerguide.org/>.

Memorial Sloan-Kettering Cancer Center. <http://www.mskcc.org/>.

National Breast Cancer Coalition. <http://www.natlbcc.org/>.

National Cancer Institute. <http://cancernet.nci.nih.gov/>.

L. Fleming Fallon, Jr., M.D., Dr.P.H.