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Cancer (medicine).

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Cancer (medicine). I INTRODUCTION Cancer (medicine), any of more than 100 diseases characterized by excessive, uncontrolled growth of abnormal cells, which invade and destroy other tissues. Cancer develops in almost any organ or tissue of the body, but certain types of cancer are more life-threatening than others. In the United States and Canada cancer ranks as the second leading cause of death, exceeded only by heart disease. Each year, about 1.7 million Americans and more than 150,000 Canadians are diagnosed with cancer, and more than half a million Americans and about 70,000 Canadians die of the disease. For reasons not well understood, cancer rates vary by gender, race, and geographic region. For instance, more men than women develop cancer, and African Americans are more likely to develop cancer than people of any other racial group in North America. The frequency of certain cancers also varies globally. For example, breast cancer is more common in wealthy countries, and cervical cancer is more common in poor countries. Although people of all ages develop cancer, most types of cancer are more common in people over the age of 50. Cancer usually develops gradually over many years, the result of a complex mix of environmental, nutritional, behavioral, and hereditary factors. Scientists do not completely understand the causes of cancer, but they know that certain lifestyle choices can reduce the risk of developing many types of cancer. Not smoking, eating a healthy diet, and exercising moderately for at least 30 minutes each day can lower the likelihood of developing cancer. Just 60 years ago a cancer diagnosis carried little hope for survival because doctors understood little about the disease and how to control it. Today about two-thirds of all Americans diagnosed with cancer live longer than five years. While it is difficult to claim that a cancer patient is disease free, long-term survival significantly improves if the patient has had no recurrence of the cancer for five years after the initial diagnosis. For years, death rates from cancer were rising in developing countries. In 2006 the American Cancer Society reported that the number of cancer deaths in the United States dropped for two years in a row. The decrease was attributed to a decline in smoking, earlier detection, and improved treatment. The National Cancer Institute of the United States (NCI) estimates that more than 10 million Americans are living with cancer or have been cured of the disease thanks largely to advances in detecting cancers earlier. The sooner cancer is found and treated, the better a person's chance for survival. In addition, advances in the fundamental understanding of how cancer develops have reduced deaths caused by certain cancers and hold promise for new and better treatments. II HOW CANCER DEVELOPS A healthy human body is composed of 30 trillion cells, most of which are in constant turnover as cells die and others reproduce to replace them in an orderly fashion. Healthy cells of the skin, hair, lining of the stomach, and blood, for example, regularly reproduce by dividing to form two daughter cells (see Mitosis). This cell division cycle proceeds under the regulation of the body's intricately tuned control system. Among other functions, this control system ensures that cells only divide when needed, so that organs and tissues maintain their correct shape and size. Should this system fail, a variety of backup safety mechanisms prevent the cell from dividing uncontrollably. In order for a cell to become cancerous, every one of these safety mechanisms must fail. Cancer begins in genes, bits of biochemical instructions composed of individual segments of the long, coiled molecule deoxyribonucleic acid (DNA). Genes contain the instructions to make proteins, molecular laborers that serve as building blocks of cells, control chemical reactions, or transport materials to and from cells. The proteins produced in a human cell determine the function of each cell, and ultimately, the function of the entire body. In a cancerous cell, permanent gene alterations, or mutations, cause the cell to malfunction. For a cell to become cancerous, usually three to seven different mutations must occur in a single cell. These genetic mutations may take many years to accumulate, but the convergence of mutations enables the cell to become cancerous. A Safety Systems Fail While each human cell performs its own specialized function, it also exerts influence on the cells around it. Cells communicate with one another via receptors, protein molecules on the cell surface. A cell releases chemical messages, which fit into the surface receptors of cells nearby, much as a key fits into a lock. A cell may instruct other cells in its neighborhood to divide, for example, by releasing a growth-promoting signal, or growth factor. The growth factor binds to receptors on adjacent cells, activating a message within each individual cell. This message travels to the nucleus, where a cell's genes are located. A1 Proto-Oncogenes Become Oncogenes When the growth factor message reaches the cell nucleus, it activates genes called proto-oncogenes. These genes produce proteins that stimulate the cell to divide. In cancerous cells, mutations in proto-oncogenes cause these genes to malfunction. When a proto-oncogene mutates, it becomes an oncogene--a gene that instructs the cell to grow and divide repeatedly without stimulation from neighboring cells. Some oncogenes overproduce growth factors, causing the cell to divide too often. Other oncogenes stimulate the cell to reproduce even when no growth factor is present. Cancer researchers have identified about 100 different types of proto-oncogenes and their cancer-causing oncogene counterparts. A2 Tumor Suppressor Genes Stop Working When runaway cell division occurs, it does not necessarily lead to cancer. Neighboring cells respond by excreting a growth inhibitor. This chemical binds to receptors in the malfunctioning cell, sending a signal to the nucleus that activates tumor suppressor genes. Tumor suppressor genes are like brakes for cell growth. When activated, these genes halt the cell cycle, preventing further cell division. But if tumor suppressor genes malfunction due to mutations, the rapidly dividing cell ignores messages from its neighbors telling it to stop dividing. Malfunctioning tumor suppressor genes are not enough to cause cancer--the cell still must overcome a host of other safety mechanisms before it can cause truly significant damage. A3 Cell Cycle Clock Malfunctions The cell nucleus contains a collection of interacting proteins that control cell division. Sometimes called the cell cycle clock, this group of proteins interprets incoming messages at several checkpoints in the cell division cycle. At these checkpoints, the clock evaluates the health of the cell. If conditions are right, the clock activates certain proto-oncogenes, which produce proteins that trigger the cell to enter the next stage of the cell cycle. If conditions are not right, certain tumor suppressor genes produce proteins that prevent the cell from proceeding with cell division. If the cell cycle clock detects DNA damage in a cell, a tumor suppressor gene called p53 prevents the cell from reproducing until the damage is repaired. If the cell is unable to repair the DNA damage, p53 instructs the cell to undergo programmed cell death, or apoptosis, putting a stop to runaway cell division before it starts. Programmed cell death is a normal part of cell life and is tightly controlled by many genes, primarily p53. In a cancerous cell, one or more mutations prevent these genes from doing their jobs. When mutated, p53 allows a cell to continue to divide, even with damaged DNA. This can lead to additional mutations in proto-oncogenes or tumor suppressor genes. In some cases, mutations occur in genes that produce proteins to repair damaged DNA. Such mutations can lead to yet other mutations because the faulty DNA cannot duplicate properly during cell division. A4 Cells Achieve Immortality A normal cell has a life span of about 40 cell divisions. This life span is controlled in part by telomeres, protective segments at the ends of the cell's DNA. Telomeres shorten with each cell division until they can no longer protect the DNA. At this point cell division severely damages the DNA, ultimately killing the cell. This normal process ensures that older cells, which may have accumulated mutations, no longer reproduce. Cancer cells escape this protective mechanism by producing a protein called telomerase. Telomerase extends the length of telomeres indefinitely, rendering the cells immortal and capable of never-ending cell division. B Cells Break Free and Spread Evading the many obstacles that guard against runaway cell division is still not enough for cancer to develop. A malfunctioning cell must also skirt a number of safety mechanisms designed to prevent cells from growing where they are not supposed to in the body. Normal cells adhere to each other and to a fibrous meshwork called an extracellular matrix. This matrix exists throughout all tissues and provides the structural support on which cells grow and form organs and other complex tissues. While a normal cell will often die if it cannot adhere to an extracellular matrix, cancer cells survive without this matrix. B1 Tumor Forms A tumor is a mass of cells not dependent upon an extracellular matrix. These cells can grow on top of each other, creating a mass of abnormal cells. Often a tumor develops its own network of tiny blood vessels to supply itself with nutrient-rich blood, a process called angiogenesis. There are two general types of tumors. Benign tumors do not invade other tissues and are limited to one site, making surgical removal possible and the odds for a full recovery excellent. Some benign tumors are quite harmless and are not surgically removed unless they are unsightly or uncomfortable. For example, warts are benign tumors of the outer layer of the skin. Although they are usually not dangerous, warts may cause discomfort. Other benign tumors are thought to be precursors to cancerous, or malignant, tumors. B2 Tumors Spread Tumors are malignant only if they can invade other parts of the body. Malignant tumors extend into neighboring tissue or travel to distant sites, forming secondary growths known as metastases. To metastasize, tumor cells break through a nearby blood vessel to enter the circulatory system or through a lymphatic vessel wall to enter the lymphatic system. Most metastases occur in organs that are the next site downstream in the circulatory system or the lymphatic system and contain a network of capillaries, or small blood vessels. For example, cancer of the large intestine often travels through the bloodstream to the liver, the organ immediately downstream from the intestines. In the lymphatic system, tumor cells can spread to surrounding lymph nodes, or lymph glands. Normally, lymph nodes filter out and destroy infectious materials circulating in the lymphatic system. The unique receptors on the surface of a cell may also play a role in where tumors metastasize. Specialized molecules on a cell's surface identify where in the body the cell belongs. Similar cells adhere to one another when their surface receptors are compatible. Most often cells from different tissues and organs have incompatible surface receptors. However, some tissue types share similar surface receptors, enabling cancerous cells to move between them and proliferate. Prostate cells and bone cells, for example, have similar surface receptors. This gives prostate cancer cells a natural affinity for bone tissue, where they can settle to form a new tumor. Many cancers shed cells into the bloodstream early in their growth. Most of these cells die in the bloodstream, but some lodge against the surface of the blood vessel walls, eventually breaking through them and into adjacent tissue. In some cases, these cells survive and grow into a tumor. Others may divide only a few times, forming a small nest of cells that remain dormant as a micrometastasis. They may remain dormant for many years, only to grow again for reasons not yet known. III CAUSES OF CANCER Scientists do not fully understand the causes of cancer, but studies show that some people are more likely to develop the disease than others. Scientists called epidemiologists study particular populations to identify why cancer rates vary (see Epidemiology). One method they use is to compare cancer patients with healthy people in terms of behavior such as diet, exercise, and smoking and traits such as gender, age, and race. Population studies provide useful information about risk factors that increase the likelihood of developing cancer. A Carcinogens One of the greatest risk factors for cancer is prolonged or repeated exposure to carcinogens--chemical, biological, or physical agents that cause the cellular damage that leads to cancer. The details of how carcinogens cause cancer remain unclear. One theory is that exposure to carcinogens, when combined with the effects of aging, causes an increase in chemicals in the body called free radicals. An excessive number of free radicals causes damage by taking negatively charged particles called electrons from key cellular components of the body, such as DNA. This may make genes more vulnerable to the mutating effects of carcinogens. A1 Tobacco Smoke Smoking causes up to 30 percent of cancer deaths in the United States and Canada, making tobacco smoke the most lethal carcinogen in North America. Smoking is associated with cancer in the lungs, esophagus, respiratory tract, bladder, pancreas, and probably cancers of the stomach, liver, and kidneys. The risk of cancer increases depending on the number of cigarettes smoked per day, the cigarette's tar content, and how many years a person smokes. Starting to smoke while young significantly increases the risk of developing cancer. Each year in the United States, several thousand nonsmoking adults die of lung cancer caused by exposure to the smoke of others' cigarettes, called secondhand smoke or environmental tobacco smoke. Nonsmoking spouses of smokers are 30 percent more likely to develop lung cancer than those married to nonsmokers. Breathing secondhand smoke also increases the risk of cancer in the children of smokers and in nonsmokers who work in smoky places. For this reason smoking has been banned in many places such as restaurants and bars. Cigars, pipes, and smokeless tobacco have also been implicated in increased risk for cancer. Cigars contain most of the same cancer-producing chemicals as cigarettes, and people who smoke cigars have a 30 percent higher risk of developing cancer than nonsmokers. Oral cancers occur more frequently in people who use smokeless tobacco, or snuff. Snuff users, for example, are 50 times more likely to develop cancers of the cheek or gum than nonusers. A2 Diet Diet can also contribute to cancer. Saturated fats from red meats, such as hamburger or steak, and high-fat dairy products are linked with several cancers. High salt intake increases the risk of stomach cancer. Adult obesity increases the risk for cancer of the uterus in women and also appears to increase the risk for cancers in the breast, colon, kidney, and gallbladder. Alcohol consumption increases the risk of cancer of the esophagus and stomach, especially when combined with smoking. A3 Pathogens Some carcinogens are living organisms. Certain viruses, bacteria, and parasites account for about 15 percent of all cancer deaths in the United States. Cancer-causing viruses include the human papillomavirus (HPV), a sexually transmitted virus responsible for 70 to 80 percent of all cases of cancer of the cervix. Hepatitis B and C viruses cause almost 80 percent of all liver cancer in the world. Epstein-Barr virus can also be carcinogenic, causing cancer of the lymphatic system. Human immunodeficiency virus (HIV) or a type of herpesvirus can lead to rare cancers of the lymphatic and circulatory systems. Helicobacter pylori, a bacterium associated with stomach ulcers, likely causes cancer of the stomach. Researchers have linked a polyomavirus to a rare, aggressive form of skin cancer called Merkel cell carcinoma. In developing countries, parasitic organisms are major carcinogens. In parts of Africa, China, and southern Asia, infestation with the liver fluke Clonorchis sinensis causes a form of liver cancer. In North Africa, infection with the parasite Schistosoma haematobium causes cancer of the bladder. A4 Radiation Exposure to electromagnetic radiation, invisible, high-energy light waves such as sunlight and X rays, accounts for a small percentage of cancer deaths (see Radiation Effects, Biological). Most cancer deaths from radiation are from skin cancer, which is triggered by too much sun exposure. Sunlight that reaches the Earth's surface contains two kinds of ultraviolet (UV) radiation. UV-A and UV-B both contribute to sunburn and skin cancer as well as to conditions such as premature wrinkling of the skin. Depletion of the ozone layer, which absorbs ultraviolet radiation in the upper atmosphere, will continue to increase skin damage and skin cancer rates in the future. Radon, a colorless, odorless, radioactive gas, seeps from the Earth in some regions of the United States. Breathing the gas over a long period has been linked to a small number of lung cancer cases. Providing adequate air circulation in a building reduces exposure to radon. Infrequently, radiation exposure associated with medical treatments, such as therapeutic radiology, leads to cancer. A5 Environmental and Occupational Chemicals Air pollution, water pollution, and pollutants in the soil contribute particularly to lung and bladder cancer. Lung cancer rates are generally higher in cities, where increased industry and automobile traffic produce air pollution. Some people encounter carcinogenic chemicals in their working environment. Occupational carcinogens include such industrial chemicals as benzene, asbestos, vinyl chloride, aniline dyes, arsenic, and certain petroleum products (see Occupational and Environmental Disease). B Hereditary Factors Evidence suggests that heredity plays a role in developing cancer. Some gene mutations associated with cancer are inherited. For example, inheriting mutated tumor suppressor genes BRCA1 or BRCA2 greatly increases a woman's chances of developing breast cancer. About 50 to 60 percent of women with inherited BRCA1 or BRCA2 mutations will develop breast cancer by the age of 70. Inherited mutations in the genes MSH2, MLH1, PMS1, and PMS2, all of which repair DNA, are especially prevalent in a rare form of hereditary colon cancer. Scientists suspect that many other hereditary factors contribute to cancer. In addition to inherited mutations, other genetic variations, particularly those influencing how the body responds to carcinogens, may create a greater susceptibility to cancer. The identities of the majority of these genetic variations are not yet known. C Steroid Hormones Medical research suggests that cancers of the reproductive organs may be affected by naturally occurring steroid hormones produced by the endocrine system. These hormones stimulate reproductive organ cells to divide and grow. In women, relatively high or long exposure to the female sex hormone estrogen seems to increase the risk of breast and uterine cancers. Thus, early age at first menstruation, late age at menopause, having a first child after age 30, and never having children, all of which affect the duration of estrogen exposure in the body, increase the risk for these cancers. Studies also indicate that hormone replacement therapy (HRT), in which women take estrogen to offset the unpleasant effects of menopause, increases the risk of breast cancer. Male sex hormones, particularly testosterone, appear to play a role in cancers of the male reproductive organs, but this role is not yet well understood. D Population Demographics Population studies show that a person's age, race, and gender affect the probability that he or she will develop cancer. Most cancers occur in adults middle-aged or older. The risk of cancer increases as individuals age because genetic mutations accumulate slowly over many years, and the older a person is, the more likely that he or she will have accumulated the collection of mutations necessary to turn an otherwise healthy cell into a cancerous cell. More than three-fourths of all cancers in North America are diagnosed in people over age 55. Statistics show that men are more likely to develop cancer than women. In the United States, nearly half of all men will develop cancer at some point in their lifetimes, whereas slightly more than one-third of women will. Cancer statistics for Canada are similar. Stomach cancer is nearly twice as common in men as in women, as are certain types of kidney cancer. However, the reasons for the discrepancy between the sexes are unknown. Some cancers are more prevalent in particular races than others. In the United States, for example, bladder cancer is twice as common in white people as in black people. White women are slightly more likely to develop breast cancer than are black women, but black women are more likely to die of the disease. Asian, Hispanic, and Native American women have the lowest breast cancer risk. On the whole, African Americans, especially men, are more likely to develop cancer--and more likely to die from it--than members of any other group in the United States. Reasons for the discrepancies between races are still not entirely clear, but many epidemiologists trace them to differences in diet and exercise, unequal access to medical care, and exposure to carcinogens. IV TYPES OF CANCER More than 100 types of cancer develop in the various organs in the body. Cancers are described according to where in the body the cancer originated, what type of tissue it originated in, and what type of cell it started in. For example, breast cancer describes any cancer that originated in the breast. If the cancer spreads to a new organ, such as the lungs, the tumor is called metastatic breast cancer, not lung cancer. Each organ in the body is composed of different types of tissue, and most cancers arise in one of three main types--epithelial, connective, or blood-forming tissue. Carcinomas are cancers that occur in epithelial tissues--the skin and inner membrane surfaces of the body, such as those of the lungs, stomach, intestines, and blood vessels. Carcinomas account for approximately 90 percent of human cancers. Sarcomas originate in connective tissues--such as muscle, bone, cartilage, and fat--that support and connect other parts of the body. Much rarer than carcinomas, sarcomas account for less than 2 percent of all cancers. Leukemias develop in blood cells, and lymphomas originate in the lymphatic system. Combined, these cancers of the blood-forming tissues account for about 8 percent of all human cancers. Cancers are further identified according to the type of cell affected. For example, squamous cells are flat, scalelike cells found in epithelial tissue. Cancers that originate in these cells are called squamous cell carcinomas. Adenomatous cells are glandular or ductal cells, and carcinomas that originate in these cells are called adenocarcinomas. Sarcomas that develop in fat cells are called liposarcomas, and those that develop in bone cells are called osteosarcomas. A Prostate Cancer Cancer of the prostate gland, a walnut-sized organ surrounding the urethra in men, is the most common cancer among men in North America, after skin cancer. For unknown reasons, the prevalence in black men is nearly twice as high as in white men. Prostate cancer risk increases with age, and some evidence suggests that highfat diets may increase the risk of developing the disease. Most prostate cancers are adenocarcinomas, cancers that arise in glandular cells of the prostate's epithelial tissue. Prostate cancers usually progress slowly and produce no symptoms in the initial stages. Eventually, the tumor may enlarge the prostate gland, pressing on the urethra and causing painful or frequent urination and blood in the urine or semen. Sometimes pain in the lower back, pelvis, or upper thighs may signal that prostate cancer cells have spread to the ribs, pelvis, and other bones. All these symptoms, however, may have other causes, such as infection of the prostate or prostate enlargement, a natural result of the aging process. The prognosis for men diagnosed with prostate cancer is excellent if it is caught and treated early. B Breast Cancer Breast cancer is the most common type of cancer in women, and the second most common cancer in North America. The majority of cases occur in women over 50, and as with most cancers, the risk of developing breast cancer increases with age. An American woman who lives to age 90 has a one in eight chance of developing breast cancer. Breast cancer strikes men as well as women, but male breast cancer accounts for less than 1 percent of all breast cancer cases. Cancer researchers have found that approximately 5 percent of all breast cancer cases are associated with inherited mutations in genes such as BRCA1, BRCA2, and p53. The protein HER-2 (also called HER2/neu), produced by oncogenes, is present in about one-third of all breast cancers. Other risk factors include a family history of the disease, early onset of menstruation, late menopause, never having children, or having a first child after age 30, conditions that extend the duration of estrogen exposure in the body. In 2006 researchers reported a 7 percent decrease of the incidence of breast cancer in the United States from 2002 to 2003. They attributed this decrease to declining use of hormone replacement therapy, which many women took to lessen the effects of menopause. A study linking HRT with an increased risk of breast cancer, reported in 2002, caused many women to stop using the therapy. Most breast cancers are first detected as an unusual mass or lump in the breast. If the cancer is detected and treated early, the odds of recovering from breast cancer are extremely good. C Lung Cancer Lung cancer is the third most common type of cancer in North America. Although it ranks below prostate cancer and breast cancer in prevalence, lung cancer is the leading cause of cancer deaths among both men and women in the United States and Canada. The death rate from lung cancer is declining among The five-year survival rate for lung cancer is quite low, but it climbs to about 50 percent if the cancer is detected early. The single largest risk factor for lung cancer is cigarette smoking, a behavior that accounts for 85 to 90 percent of all cases. The incidence of lung cancer, as well as the death rate, is declining among North American men as a result of the drop in smoking. Lung cancer rates have been increasing among women, who took up smoking in large number during and after World War II. The lung cancer incidence and death rate among North American women has now reached a plateau and is expected to decline, as more and more women have ceased to smoke. Long-term exposure to secondhand smoke also causes lung cancer. Other major risk factors include workplace exposure to carcinogenic chemicals, particularly asbestos and organic chemicals such as vinyl chloride. Exposure to radon gas and other air pollutants also increases lung cancer risk, particularly among smokers. Lung cancer often goes unnoticed in its early stages. As the disease develops, a persistent cough may develop or a chronic cough may worsen. Other symptoms include chest pain, shortness of breath, hoarseness, bloody fluid coughed up from the respiratory tract, and frequent bouts of bronchitis or pneumonia. Sometimes the first symptoms of lung cancer are bone pain, headaches, dizziness, or other signs that the disease has metastasized. D Colorectal Cancer Colorectal cancer, cancer of the large intestine, is the fourth most common cancer in North America. Many cases of colorectal cancer are associated with low levels of physical activity and with diets that are low in fruits and vegetables. Individuals with a family history of the disease have a higher risk. High rates of colorectal cancer are also found in people who have colorectal polyps, fleshy growths on the inside lining of the large intestine, and in those who have inflammatory bowel disease, a condition causing pain and inflammation of the small intestine or the colon. Colorectal cancer usually develops slowly and may not produce noticeable symptoms in its early stages. Some individuals with undiagnosed colorectal cancer may detect blood in their feces. They may also experience persistent constipation or diarrhea, abdominal pain, or unexplained weight loss. Eventually the tumor may grow so large that it obstructs the intestine or causes it to rupture. Screening tests can detect precancerous intestinal polyps and colorectal cancer in an early, and easily treatable, stage. E Lymphoma Lymphoma encompasses a group of related cancers that arise in the lymphatic system, organs and cells of the body involved in fighting infection. Lymphomas are classified as non-Hodgkin's lyphoma or as Hodgkin's disease, a cancer named after British physician Thomas Hodgkin who first described it in 1832. Non-Hodgkins lymphomas generally develop in white blood cells known as lymphocytes that are critical to the functioning of the immune system. Lymphocytes travel throughout the body and thus can spread lymphoma to other organs where they destroy healthy tissue. The most common symptom of lymphoma is a painless swelling in the lymph nodes in the neck, underarm, or groin. Other symptoms include fevers, night sweats, tiredness, weight loss, itching, and reddened patches on the skin. Sometimes there is nausea, vomiting, or abdominal pain. Lymphoma risk increases with age and with decreasing immune function, such as that caused by acquired immunodeficiency syndrome (AIDS) or exposure to certain infectious agents. Organ transplant recipients are at increased risk of lymphoma because they take drugs that weaken the immune system as part of the transplantation process (see Medical Transplantation). Although the symptoms of Hodgkin's disease are similar to symptoms of other lymphomas, the cancer cells of the two look different under a microscope, and they grow and spread in different ways. Non-Hodgkin's lymphoma is more prevalent than Hodgkin's disease, but Hodgkin's disease is easier to treat and less severe. The five-year survival rate is more than 80 percent for Hodgkin's disease and more than the 60 percent for non-Hodgkin's lymphoma. F Bladder Cancer Bladder cancer affects white Americans at almost twice the rate of African Americans, and men are two to three times more at risk than women. The disease is also more likely to affect smokers than nonsmokers. Occupational exposures also appear to increase risk. People who work in the rubber, leather, and chemical industries are at greater risk, as are hairdressers, machinists, metal workers, printers, painters, and textile workers. Chemicals used in these industries become concentrated in the urine, causing bladder cells to become cancerous. Bladder tumors may obstruct urine flow into the bladder or interfere with bladder function in other ways. When symptoms are present, they may include blood in the urine and painful or frequent urination. The prognosis is generally excellent when a bladder tumor is detected early. G Uterine Cancer Uterine cancer includes both cervical cancer and endometrial cancer, cancer of the lining of the uterus. The single greatest risk factor for cervical cancer is infection with the human papillomavirus (HPV). The risk increases for women who smoke cigarettes or have many sexual partners. For reasons that are not entirely clear, the disease also seems to be more common in women of low socioeconomic status. Most cervical cancers develop slowly and may not produce any noticeable symptoms in the early stages. As the cancer progresses, the woman may experience a watery vaginal discharge and painless bleeding. Over time, the bleeding becomes heavier and more frequent, and pain becomes noticeable in the lower abdomen or back. The prognosis for cervical cancer patients in the United States is generally excellent if the cancer is detected early. For unknown reasons, however, black women in the United States are twice as likely to die of the disease as are white women. The risk of developing endometrial cancer appears to be related to a woman's exposure to the hormone estrogen. Thus, early onset of menstruation or late menopause increase a woman's risk, probably by increasing the number of years during which the endometrium is exposed to estrogen. Obesity also increases the risk of endometrial cancer, probably because excess fat can increase estrogen levels in a woman's body. Tamoxifen, a drug used for preventing breast cancer, acts like estrogen on cells of the endometrium and raises the risk of endometrial cancer. Endometrial cancer symptoms are similar to those of cervical cancer. Most often, they start with a vaginal discharge that has streaks of blood. The prognosis for endometrial cancer patients is generally excellent if the cancer is caught and treated at an early stage. H Skin Cancer There are three main types of skin cancer: basal cell carcinoma, squamous cell carcinoma, and melanoma. While basal cell and squamous cell carcinomas account for by far the largest percentage of skin cancers, melanoma is the most dangerous type and accounts for almost of the deaths due to skin cancer. The single greatest risk factor is exposure to sunlight, especially during childhood. Melanoma occurs more frequently in people with fair skin and freckles. Symptoms include any change in the size, shape, color, or texture of a mole or other darkly pigmented area of the skin. Any mole that begins to itch or becomes tender may be a sign of skin cancer. Other signs include sores that do not heal or black spots under a toenail or fingernail that extend beneath the cuticle. Melanoma begins in cells that produce the skin pigment melanin, but it is likely to spread to other parts of the body. Skin cancer is only of the most treatable cancers, with an extremely high survival rate--even for melanoma--if detected early. I Kidney Cancer Men have nearly a 50 percent greater risk than women of developing cancer of the kidney, and smokers have a 40 percent greater risk than nonsmokers. Excess weight and high blood pressure also increase the risk of developing kidney cancer. Some studies show a link between occupational exposure to asbestos or cadmium and kidney cancer. Kidney cancer is rare in people under age 45. However, a type of cancer known as Wilms' tumor develops in children when the kidney cells fail to mature and instead divide uncontrollably, forming a mass of immature cells. Kidney tumors can become quite large before causing any symptoms. The most common symptom of kidney cancer is blood in the urine. A lump or a mass that can be felt in the kidney area may also be an indication of kidney cancer. As kidney cancer grows, it may invade organs near the kidney, such as the liver, colon, or pancreas. J Leukemia Leukemia is a cancer of the bone marrow and blood cells. Leukemia is typically thought to be a childhood disease, but in fact it strikes many more adults. Smoking increases the risk of developing leukemia, as does long-term exposure to high levels of the chemical benzene and exposure to high doses of radiation. There are four types of leukemia, classified by the type of blood cell affected and whether the cells are mature or immature. The four major types are acute myelocytic leukemia (AML), chronic myelocytic leukemia (CML), acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL). AML and CLL are most common in adults, while ALL is the most common form in children. CML also affects adults. Acute leukemias progress rapidly, while chronic leukemias tend to develop slowly. Most symptoms of leukemia result from a deficiency of normal blood cells that occurs when leukemia cells accumulate and crowd out these cells. General symptoms include weight loss, fever, and loss of appetite, and less often, profuse bleeding from the gums and mucous membranes under the skin. Low levels of red blood cells may also indicate the presence of leukemia. The five-year survival rate for people with leukemia has greatly improved in the United States over the past several decades. The prognosis varies according to the type of leukemia and the age of the patient. AML is the most dangerous of the leukemias, with the lowest five-year survival rate. K Pancreatic Cancer Pancreatic cancer involves the pancreas , a small gland sandwiched between the stomach and intestine that secretes chemicals used in digestion. Epidemiologists estimate that smoking causes about 30 percent of all cases of pancreatic cancer. Men are more likely to develop this type of cancer than women, and in the United States, pancreatic cancer affects African Americans more than any other ethnic group. Although rarer than many types of cancer, pancreatic cancer is the fourth leading cause of cancer death in the United States because it produces few if any symptoms before it metastasizes. Lung cancer, colorectal cancer, and breast cancer surpass it in cancer-related deaths. When symptoms of the disease are present, they may include jaundice, a yellowing of the skin, eyes, and fingernails; abdominal pain; weight loss; and digestive problems. Usually by the time symptoms appear, the cancer has spread to distant organs in the body. For this reason, the prognosis for people diagnosed with pancreatic cancer is generally poor. L Ovarian Cancer About two-thirds of the cases of ovarian cancer in the United States and Canada occur in women over the age of 55. Women who have had breast cancer or have a family history of ovarian cancer are at increased risk of developing ovarian cancer, as are women with inherited mutations in the tumor suppressor genes BRCA1 and BRCA2. Other conditions that increase the risk for ovarian cancer include early age at first menstruation, late menopause, having a first child after age 30, or having no children at all. While relatively rare, ovarian cancer often does not produce symptoms and thus goes undiagnosed until the cancer has spread and become more deadly. At that point, a woman may experience any of a variety of symptoms, such as an enlarged abdomen, persistent abdominal discomfort, indigestion, nausea or vomiting, weight loss, diarrhea or constipation, and bleeding that is not part of a normal menstrual period. M Stomach Cancer Stomach cancer is more common in men than in women, and it occurs much more frequently in people who have experienced long-term infection with the Helicobacter pylori bacterium. Incidence of stomach cancer varies significantly among different populations. For example, the disease is far more common in Japan than in the United States. Researchers attribute these regional differences to dietary differences. Diets high in smoked or cured meats appear to increase the risk of stomach cancer. In the United States, stomach cancer is now far less common than it was in 1930. This decline may be due, in part, to widespread use of refrigeration for food storage and, as a consequence, decreased consumption of salted and smoked foods. Like many cancers of the internal organs, stomach cancer rarely produces noticeable symptoms until it has spread to other sites in the body. When symptoms are present, they may include abdominal pain, heartburn, nausea, and vomiting. Stomach cancer is rarely detected early, and the prognosis for people diagnosed with stomach cancer has improved only slightly in recent decades. V DIAGNOSIS Diagnosis of cancer often begins when a person notices an unusual health symptom and consults a doctor. Early warning signs of cancer include changes in bowel or bladder habits, a sore that does not heal, unusual bleeding or discharge, thickening or a lump in the breast or any other part of the body, indigestion or difficulty swallowing, change in appearance of a wart or mole, or a nagging cough or hoarseness. A Detection People with early warning signs should consult their family doctor, who will evaluate symptoms and may refer the patient to a physician who specializes in cancer. A physician will first take the patient's medical history to learn about current symptoms, past history of disease, and family members diagnosed with cancer. The procedures used in a physical exam depend on the patient's clinical symptoms and may include a digital rectal examination, in which the physician uses a gloved finger to gently check the smoothness of the rectal lining. The physician may perform a breast exam on female patients, in which the breasts are gently probed to feel for lumps or unusual masses. During the examination the physician may use a thin, lighted tube called an endoscope to look for tumors in internal body cavities. The endoscopy procedure used depends on the organ or body cavity examined. In gastric endoscopy, the doctor feeds a specialized endoscope down the throat to examine the lining of the esophagus, stomach, and first part of the small intestine. Fiberoptic sigmoidoscopy, in which a flexible instrument is inserted into the lower intestinal tract through the anus, enables a physician to visually examine the interior of the colon and rectum. Colonoscopy uses a much longer flexible instrument to view the entire length of the large intestine. A number of laboratory tests help narrow the possible diagnoses. In a Pap smear, cells are removed from the cervical epithelium with a small plastic brush. These cells are examined under a microscope for cell changes that are a sign that cancer may be developing as well as signs of malignancy. If a patient's clinical signs suggest colorectal cancer, the doctor may search for blood in the stool using a fecal occult blood test. A small sample of the patient's stool is smeared on a card coated with a chemical called guaiac, which reacts with blood. The card is analyzed in a laboratory for occult (hidden) blood. Certain blood tests determine if levels of red and white blood cells are low, a possible indication of leukemia. Others test for the presence of tumor markers, chemicals that are present in higher levels when certain cancers are present. For example, a prostate-specific antigen (PSA) test measures levels of prostate-specific antigen in the blood. Prostate cancer cells overproduce this protein, causing an elevation of PSA levels in blood. Medical imaging techniques help doctors locate and evaluate a tumor. These include computed tomography (CT) and magnetic resonance imaging (MRI) scans. CT and MRI scans use computers to form a three-dimensional image of the tumor and surrounding tissues. X-ray images of the breast called mammograms help physicians detect and evaluate breast cancer. Ultrasound scanning bounces high-frequency sound waves off a tumor and surrounding tissue to create an image of the tumor. The multimodality display technique combines the images from several imaging tools into one picture, providing a final three-dimensional image with much greater detail. Computer-aided diagnosis uses complex computer programming technology called artificial intelligence to scan mammograms and X rays to help look for signs of cancer and offer an automated second opinion. B Staging When a tumor is detected, the physician takes a biopsy by removing a sample of the tissue. The biopsy sample is inspected under a microscope to determine if the tumor is benign or malignant. Cancerous cells usually appear abnormal in shape and no longer orient themselves in orderly configurations. If the tumor is cancerous, the physician assigns it a stage, indicating how far cancer has spread. The stage is a key factor in determining both the cancer's treatment and prognosis. Oncologists, physicians who specialize in the diagnosis and treatment of cancer, use several different staging systems. In one system, tumors are grouped into four stages denoted by Roman numerals I through IV. Stage I cancers are small localized cancers that are usually curable. Stage II and III tumors are usually locally advanced and may or may not have invaded nearby lymph nodes, and stage IV tumors have usually metastasized--that is, spread to distant tissues in the body. The most widely used staging system is the Tumor, Lymph Node, and Metastasis system, commonly abbreviated TNM. This system uses numbers between zero and three to assess the size of the tumor (T), the extent that it has spread to nearby lymph nodes (N), and the extent that it has spread throughout the body (M). A cancer's stage depends on a combination of these numbers. For example, a T-1, N-0, and M-0 tumor is a stage 1 tumor. This tumor is 2 cm (1 in) or less (T-1) and has not spread to nearby lymph nodes (accounting for N-0) or metastasized (M-0). The five-year survival rate for a patient with this stage tumor is accordingly excellent. A T-3, N-1, and M-0 tumor is a stage 3 tumor. This tumor is greater than 5 cm (2 in) and has spread to nearby lymph nodes, but there is no evidence that the cancer has spread to distant tissues. The five-year survival rate for a patient with this tumor is not as high as the T-1, N-0, M-0 patient. Stage 4 tumors are distinguished by an M1 number. This means they have progressed to the point where metastasis is widespread, and the prognosis is usually quite poor. VI TREATMENT Oncologists select from a number of options when treating cancer, depending on the type and stage of the tumor involved. The major treatments currently available are surgery, radiation therapy, chemotherapy, hormone therapy, and immunotherapy. Often, targeting cancerous tumors requires the artful combination of more than one type of cancer therapy. A Surgery Surgery is the most effective and fastest treatment for tumors that are caught early and have not metastasized. It is the only option ensuring that the entire visible tumor is eliminated. However, there is no guarantee that all microscopic extensions of a tumor have been removed. For this reason, surgeons may also remove a large portion of healthy tissue that surrounds the tumor. This may not be possible if the tumor lies near or within a vital tissue, such as a major nerve or organ. Often, cancer surgery requires general anesthesia, in which the patient loses consciousness, and a hospital stay of several days. For example, women with breast cancer may have a lumpectomy or mastectomy, surgical removal of part (or all) of the breast. Depending on the stage of the tumor, doctors may also remove the nearby lymph nodes and muscle tissue. As with any major surgery, mastectomies and other major surgical cancer treatments involve some risk, and doctors must consider the overall health of the patient, as well as the stage of the tumor. Some cancers can be treated surgically with less-invasive techniques, such as laser surgery. Laser surgery uses a powerful beam of high-energy light to vaporize certain tumors of the cervix, larynx, and skin. Physicians perform laser surgery with an endoscope inserted through a small incision in the skin. Laser surgery and other lessinvasive surgical procedures may require only local anesthesia, in which a patient loses feeling in one particular area of the body but never loses consciousness. Sometimes oncologists recommend surgery to improve a patient's quality of life, even if it is not likely to rid the body of cancer. Surgery of this type aims to correct a problem that is causing discomfort or disability. For example, some cancers may spread to the spine, pressing on the spinal cord or nearby nerves. This pressure may cause severe pain, and in some instances, paralysis. Surgical removal of all or part of the tumor near the spine may alleviate these symptoms. B Radiation Therapy Therapeutic radiology uses high-energy particles or waves, such as X rays or gamma rays, to focus damaging radiation on the region of a tumor, inflicting genetic damage that kills cancerous cells. Radiation therapy damages rapidly dividing cells, mostly cancer cells but also healthy cells that reproduce quickly. This leads to side effects such as fatigue, skin changes, and loss of appetite. Other side effects usually are related to the treatment of specific areas, such as hair loss following radiation treatment to the head. Radiation therapy can also cause a decrease in the number of white blood cells, cells that help protect the body against infection. Most side effects are short-lived, as healthy tissues recover from radiation much better than cancer cells because healthy cells repair damaged DNA more efficiently. Many short doses of radiation therapy, instead of fewer heavier doses, can minimize side effects. The total dose and the number of treatments depend on the size, location, and type of cancer and the patient's general health. Patients usually receive radiation therapy five days a week for five to eight weeks. Weekend rest breaks allow normal cells to recover. Unlike surgery, radiation can destroy microscopic cancer cells that have moved into surrounding tissues. Radiation is also a safer option for older patients or those weakened from other diseases, who may not recover well from surgery. Oncologists may use radiation to shrink the tumor, making surgery feasible. For other tumors, radiation may be used following surgery. However, radiation does not always eliminate all tumor cells, and it cannot treat widespread metastases. Like surgery, radiation therapy may be used to relieve pain and discomfort, even when a cure is not likely. C Chemotherapy Chemotherapy uses powerful anticancer drugs that travel through the bloodstream, making it potentially useful for cancers that have spread. Oncologists use about 50 different chemotherapeutic drugs to combat cancer, generally administering more than one drug at a time because these drugs are more powerful when combined. Taken orally or injected into the bloodstream, chemotherapeutic drugs interfere with cancer cells' ability to make new DNA or divide properly. In some cases, the drugs cause programmed cell death. Many leukemias, lymphomas, and cancers of the testicles are successfully treated with chemotherapy. Breast, lung, colorectal, and prostate cancer are not currently curable with chemotherapy alone, so chemotherapy is often used in combination with other therapies. In fact, the most common combination of cancer treatments is surgery or radiation therapy followed by chemotherapy. Chemotherapy often causes severe side effects, particularly reduced resistance to infection, internal bleeding, diarrhea, nausea, vomiting, hair loss, and insufficient oxygen in the blood, known as anemia. Some tumors develop resistance to many drugs after exposure to just one drug, a condition called multidrug resistance. When this happens, there may be no drugs that are effective against the tumor. D Hormone Therapy Some types of cancer, such as breast and prostate cancer, depend on sex hormones to grow. Hormone therapy prevents cancer cells from receiving or using the hormones they need. Hormone therapy may include surgery to remove organs in the endocrine system that make hormones. In other cases, hormone therapy relies on drugs to stop hormone production or change the way hormones work. Antiestrogen drugs, such as tamoxifen and raloxifene, given to women with breast cancer block the hormone estrogen and inhibit its ability to stimulate cell growth. Sometimes called designer estrogens, these drugs cause only mild side effects because treatment is limited to tissues affected by hormones. Androgen blockers are given to men with prostate cancer to block the production of testosterone and other male hormones that may contribute to cancer growth. E Immunotherapy Immunotherapy, also called biologic therapy, uses the body's own immune system to fight cancer cells or protect the body from side effects. Immunotherapy relies on antibodies, naturally occurring proteins dedicated to defending the body against invasion by foreign substances. In one kind of immunotherapy, antibodies are used to attack tumor cells directly, while in another approach, antibodies are used to deliver toxic agents, such as radioactive substances or drugs, which selectively target and harm cancer cells. Monoclonal antibodies are laboratory-produced antibodies used to fight many diseases, including cancer. One of the newest treatments for breast cancer is a monoclonal antibody called Herceptin, which targets cancer cells that overproduce HER-2, the protein implicated in about one-third of all breast cancers. Other forms of immunotherapy include the use of interferon, a naturally and synthetically produced protein that fights disease-causing agents in the body, particularly viruses. Interferons slow the growth of tumor cells in some patients, and they stimulate the immune system to attack cancerous cells. Another therapy, interleukin-2, is a naturally occurring immune system chemical that stimulates a type of immune cell that attacks cancer cells. Colony stimulating factors help regulate the production of white blood cells, enabling the body to better combat the disease. VII PREVENTION Scientists estimate that many cancer deaths in the United States could be prevented through lifestyle changes. Although there is no certain way to avoid all cancers, reducing individual risk factors significantly decreases the likelihood of contracting many forms of this devastating disease. A Lifestyle Changes The ACS estimates that smoking causes nearly 30 percent of all cancer deaths in the United States. These deaths could be prevented if people did not smoke or use smokeless tobacco. For those who already smoke, quitting will reduce the risk of developing cancer. Studies show that after about ten years of not smoking, a past smoker's risk lowers to about the level of those who have never smoked. Some studies suggest that eating a healthy diet, especially one rich in fruits and vegetables, can lower the risk of certain cancers. For a time it was believed that cruciferous vegetables, such as broccoli, cauliflower, and cabbage, which are high in the substance beta-carotenes called antioxidants, offered protection against some cancers. But follow-up studies that tracked the amount of beta-carotene and other antioxidants in people's diets have failed to demonstrate any protective effect. Other studies implicate diets high in fat with certain cancers, especially breast and prostate cancer. A study reported in 2005 found that a low-fat diet reduced the risk of breast cancer recurrence in women treated for early-stage breast cancer. People can lower their fat consumption by eating less red meat and fewer high-fat dairy products. Limiting consumption of alcoholic beverages to one drink a day can also lower the risk of certain cancers. Protecting the skin from the sun's rays could prevent about 80 percent of all skin cancers. When in the sun for prolonged periods, always wear sunscreen with a sun protection factor (SPF) of 15 or greater, particularly if you have fair skin or freckles. Skin needs protection every day, not just on sunny days. The Skin Cancer Foundation also recommends that people avoid the sun at its peak (from 10 AM to 4 PM), seek shade, and cover up with clothing and a brimmed hat. People also can help prevent cancer by practicing safe sex. Infection with the sexually transmitted human immunodeficiency virus (HIV) greatly increases an individual's risk for cancers of the immune and lymphatic system, such as Kaposi's sarcoma. Infection with the hepatitis B virus (HBV) is the predominant cause of liver cancer in the United States. HBV is transmitted from person to person through unprotected sexual intercourse with an infected person, or through the sharing of infected needles or other sharp instruments that break the skin. Vaccination against hepatitis B reduces the spread of this virus, which leads to reduced incidence of liver cancer. Condoms can also help prevent infection with the human papillomavirus (HPV), which is linked with cervical cancer. But a vaccine against HPV offers even better protection. B Screening and Early Detection Early detection is the best way to prevent cancer from becoming life threatening. Detecting a tumor while it is still in an early stage is the best predictor of long-term survival. Screening for colon cancer can detect and treat intestinal changes before they become cancerous and thereby prevent the disease entirely. For this reason, the ACS recommends a number of screening tests for people who do not have symptoms. A cancer-related checkup is recommended every three years for people aged 20 to 40 and every year for people over age 40. For more information about other screening tests, see the table on Cancer Screening Recommendations. In addition to regular cancer check ups, advanced technologies may help detect certain cancers. Scientists have developed tests for the presence of certain genetic mutations. People who test positive for these genetic mutations may take preventive measures such as more frequent cancer screening examinations and dietary modification to reduce their risk. Women who test positive for a mutated breast cancer gene, such as BRCA1 or BRCA2, may choose to have a mastectomy even when no cancer is present. This eliminates most breast tissue before cancer has a chance to form. The ability to determine a person's genetic risk for cancer years or even decades before it develops has raised a number of ethical, social, and psychological implications. Several government committees have published guidelines to prevent discrimination in hiring or firing employees who have had a genetic test or have tested positive for a particular cancer-causing gene. Families with high risk for cancer are also affected by the psychological implications of knowing which family members are at risk and which are not. In some cases, tests are available to identify people at risk for certain cancers, such as inherited forms of breast or colon cancers, but surefire preventive or treatment measures for these cancers have not been developed yet. While some people would prefer to know their risk for disease so they can make appropriate lifestyle changes, others prefer not to be hampered by this knowledge when no treatment exists for the problem. VIII CANCER RESEARCH Two-thirds of Americans diagnosed with cancer now survive more than five years. Survival rates for most cancers have greatly increased over the past 50 years. Between 1990 and 1995 the rate of new cancers and the death rate from cancer dropped in the United States for the first time in 20 years. In 1998 the ACS, the NCI, and the Centers for Disease Control and Prevention (CDC) confirmed that cancer rates were still on the decline. However, the actual number of cancer cases and cancer deaths continued to rise because the U.S. population was growing and aging. In 2006 cancer agencies announced that the actual number of cancer deaths had fallen for two years in a row, in 2003 and in 2004. The greatest decline in deaths occurred for colon cancer. Cancer experts attributed the decrease primarily to smoking cessation and to improved detection of colon cancers and prostate cancers, but they also credited improved treatment. These improved cancer statistics are due in part to changes in people's behavior but equally to advances in cancer research that have taken place in the last four decades. A Clinical Trials Clinical trials are research studies that use human patients to determine if a new treatment is effective. Medical and ethical panels overseen by the Food and Drug Administration (FDA) carefully review the research methods and ethics of a clinical trial before the trial begins, then monitor the trial throughout its four main phases. Phase I of a clinical trial studies a small number of patients to determine the best dosage and delivery method of a new drug treatment. Patients who participate in a Phase I trial usually have advanced cancer and would not be helped by other known treatments. Phase II, conducted with a different group of patients, determines how well the treatment actually works in different types of cancer. Phase III compares the effectiveness of the new treatment in one set of patients to another set of patients who receive the best currently available drug treatment. In Phase IV studies, the treatment becomes part of the standard treatment regimen, but it is tested for how effective it is when combined with other treatments. Researchers continually study and find new ways to treat cancer. Studies in an area of research called antimetastasis focus on halting tumor cells from spreading and invading new tissues. Other researchers study how to stop a tumor from developing its own blood supply, a process called antiangiogenesis. Two antiangiogenesis drugs, called angiostatin and endostatin, stop the growth of blood vessels and have been quite successful in treating tumors in mice. These two drugs are currently in clinical trials in humans. Several drugs that block oncogene signals are in clinical trials. Researchers are also introducing genes into immune cells that will specifically recognize and kill cancer cells. Other research is investigating the introduction of a normal gene into a tumor cell to increase the tumor's sensitivity to chemotherapeutic drugs. A growing field of cancer prevention research is chemoprevention, or the use of natural or synthetic compounds to decrease the number of mutations that may lead to cancer. Chemoprevention research seeks to identify those compounds that reduce risk and use them in pills or food additives as a prevention measure for those who are at high risk for cancer. More than two dozen chemopreventive compounds are currently being studied for how well they work in humans. B Basic Research Scientists who conduct basic research on the causes of cancer focus on the fundamental genetic mutations that underlie cancer. One goal seeks to identify all of the mutations present in a patient's tumor, enabling better prediction of the tumor's future behavior. Developing technologies use a tiny glass chip the size of a computer chip to compare DNA in tumor cells to DNA in healthy cells. This new diagnostic tool will someday help physicians to tailor the treatment of individual patients according to their tumors' genetic makeup. Since cancer is uncontrolled cell division, research into the genetic mechanisms that control normal cell division also holds promise. A better understanding of the normal function of a mutated gene may provide better insight into what goes wrong in tumor cells. This may lead to better treatments designed to combat specifically the effects of the mutation. Contributed By: Karen R. Peterson Microsoft ® Encarta ® 2009. © 1993-2008 Microsoft Corporation. All rights reserved.

« unable to repair the DNA damage, p53 instructs the cell to undergo programmed cell death, or apoptosis , putting a stop to runaway cell division before it starts. Programmed cell death is a normal part of cell life and is tightly controlled by many genes, primarily p53. In a cancerous cell, one or more mutations prevent these genes from doing their jobs. When mutated, p53 allows a cell to continue to divide, even with damaged DNA.This can lead to additional mutations in proto-oncogenes or tumor suppressor genes. In some cases, mutations occur in genes that produce proteins to repair damagedDNA. Such mutations can lead to yet other mutations because the faulty DNA cannot duplicate properly during cell division. A4 Cells Achieve Immortality A normal cell has a life span of about 40 cell divisions. This life span is controlled in part by telomeres, protective segments at the ends of the cell’s DNA. Telomeresshorten with each cell division until they can no longer protect the DNA. At this point cell division severely damages the DNA, ultimately killing the cell. This normalprocess ensures that older cells, which may have accumulated mutations, no longer reproduce. Cancer cells escape this protective mechanism by producing a proteincalled telomerase. Telomerase extends the length of telomeres indefinitely, rendering the cells immortal and capable of never-ending cell division. B Cells Break Free and Spread Evading the many obstacles that guard against runaway cell division is still not enough for cancer to develop. A malfunctioning cell must also skirt a number of safetymechanisms designed to prevent cells from growing where they are not supposed to in the body. Normal cells adhere to each other and to a fibrous meshwork called an extracellular matrix. This matrix exists throughout all tissues and provides the structural supporton which cells grow and form organs and other complex tissues. While a normal cell will often die if it cannot adhere to an extracellular matrix, cancer cells survivewithout this matrix. B1 Tumor Forms A tumor is a mass of cells not dependent upon an extracellular matrix. These cells can grow on top of each other, creating a mass of abnormal cells. Often a tumordevelops its own network of tiny blood vessels to supply itself with nutrient-rich blood, a process called angiogenesis . There are two general types of tumors. Benign tumors do not invade other tissues and are limited to one site, making surgical removal possible and the odds for a fullrecovery excellent. Some benign tumors are quite harmless and are not surgically removed unless they are unsightly or uncomfortable. For example, warts are benigntumors of the outer layer of the skin. Although they are usually not dangerous, warts may cause discomfort. Other benign tumors are thought to be precursors tocancerous, or malignant, tumors. B2 Tumors Spread Tumors are malignant only if they can invade other parts of the body. Malignant tumors extend into neighboring tissue or travel to distant sites, forming secondarygrowths known as metastases. To metastasize, tumor cells break through a nearby blood vessel to enter the circulatory system or through a lymphatic vessel wall toenter the lymphatic system. Most metastases occur in organs that are the next site downstream in the circulatory system or the lymphatic system and contain anetwork of capillaries, or small blood vessels. For example, cancer of the large intestine often travels through the bloodstream to the liver, the organ immediatelydownstream from the intestines. In the lymphatic system, tumor cells can spread to surrounding lymph nodes, or lymph glands. Normally, lymph nodes filter out anddestroy infectious materials circulating in the lymphatic system. The unique receptors on the surface of a cell may also play a role in where tumors metastasize. Specialized molecules on a cell’s surface identify where in the body thecell belongs. Similar cells adhere to one another when their surface receptors are compatible. Most often cells from different tissues and organs have incompatiblesurface receptors. However, some tissue types share similar surface receptors, enabling cancerous cells to move between them and proliferate. Prostate cells and bonecells, for example, have similar surface receptors. This gives prostate cancer cells a natural affinity for bone tissue, where they can settle to form a new tumor. Many cancers shed cells into the bloodstream early in their growth. Most of these cells die in the bloodstream, but some lodge against the surface of the blood vesselwalls, eventually breaking through them and into adjacent tissue. In some cases, these cells survive and grow into a tumor. Others may divide only a few times,forming a small nest of cells that remain dormant as a micrometastasis. They may remain dormant for many years, only to grow again for reasons not yet known. III CAUSES OF CANCER Scientists do not fully understand the causes of cancer, but studies show that some people are more likely to develop the disease than others. Scientists calledepidemiologists study particular populations to identify why cancer rates vary ( see Epidemiology). One method they use is to compare cancer patients with healthy people in terms of behavior such as diet, exercise, and smoking and traits such as gender, age, and race. Population studies provide useful information about riskfactors that increase the likelihood of developing cancer. A Carcinogens One of the greatest risk factors for cancer is prolonged or repeated exposure to carcinogens—chemical, biological, or physical agents that cause the cellular damagethat leads to cancer. The details of how carcinogens cause cancer remain unclear. One theory is that exposure to carcinogens, when combined with the effects of aging,causes an increase in chemicals in the body called free radicals. An excessive number of free radicals causes damage by taking negatively charged particles called electrons from key cellular components of the body, such as DNA. This may make genes more vulnerable to the mutating effects of carcinogens. A1 Tobacco Smoke Smoking causes up to 30 percent of cancer deaths in the United States and Canada, making tobacco smoke the most lethal carcinogen in North America. Smoking isassociated with cancer in the lungs, esophagus, respiratory tract, bladder, pancreas, and probably cancers of the stomach, liver, and kidneys. The risk of cancerincreases depending on the number of cigarettes smoked per day, the cigarette’s tar content, and how many years a person smokes. Starting to smoke while youngsignificantly increases the risk of developing cancer. Each year in the United States, several thousand nonsmoking adults die of lung cancer caused by exposure to the smoke of others’ cigarettes, called secondhand smokeor environmental tobacco smoke. Nonsmoking spouses of smokers are 30 percent more likely to develop lung cancer than those married to nonsmokers. Breathingsecondhand smoke also increases the risk of cancer in the children of smokers and in nonsmokers who work in smoky places. For this reason smoking has been banned »

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