Basal and squamous cell carcinomas are the most common types of cancer. Both arise from epithelial tissue (see epithelium). They are rare in dark-skinned people; light-skinned, blue-eyed people who do not tan well but who have had significant exposure to the rays of the sun are at highest risk. Both types usually occur on the face or other exposed areas.
Basal cell carcinoma typically is seen as a raised, sometimes ulcerous nodule. The nodule may have a pearly appearance. It grows slowly and rarely metastasizes (spreads), but it can be locally destructive and disfiguring. Squamous cell carcinoma typically is seen as a painless lump that grows into a wartlike lesion, or it may arise in patches of red, scaly sun-damaged skin called actinic keratoses. It can metastasize and can lead to death.
Basal and squamous cell carcinomas are easily cured with appropriate treatment. The lesion is usually removed by scalpal excision, curettage, cryosurgery (freezing), or micrographic surgery in which successive thin slices are removed and examined for cancerous cells under a microscope until the samples are clear. If the cancer arises in an area where surgery would be difficult or disfiguring, radiation therapy may be employed. Genetic scientists have discovered a gene that, when mutated, causes basal cell carcinoma.
Melanoma is the most virulent type of skin cancer and the type most likely to be fatal. As with the other common skin cancers, melanoma can be caused by exposure to the sun, and its incidence is increasing around the world. There also appears to be a hereditary factor in some cases. Although light-skinned people are the most susceptible, melanomas are also seen in dark-skinned people. Melanomas arise in melanocytes, the melanin-containing cells of the epidermal layer of the skin. Melanin is the pigment that gives skin color and that helps to protect the skin from sun damage. In light-skinned people, melanomas appear most frequently on the trunk in men and on the arms or legs in women. In blacks melanomas appear most frequently on the hands and feet. It is unknown whether melanoma in blacks is related to sun exposure. It is recommended that people examine themselves regularly for any evidence of the characteristic changes in a mole that could raise a suspicion of melanoma. These include asymmetry of the mole, a mottled appearance (variations in color from shades of brown to a bluish tint), irregular or notched borders, and oozing or bleeding or a change in texture. Surgery performed before the melanoma has spread is the only effective treatment for melanoma.
See publications of the National Cancer Institute and the American Cancer Society.
Traditionally, prostate cancer screening consisted of digital-rectal examination. Since 1986, however, a blood test for a tumor marker called prostate-specific antigen (PSA) has greatly increased the number of early-stage prostate cancers diagnosed. An elevated level of PSA can indicate the presence of prostatic malignancy. Elevated PSA is further investigated by an ultrasound test and needle biopsy, in which a fine needle is inserted into the gland and cells are extracted for laboratory analysis. In some cases a bone scan is also performed to rule out metastatic disease. Because PSA tests detect not only aggressive cancers but slow-growing cancers that are not life-threatening, many people disagree with routine PSA testing of asymptomatic men, fearing that the test might lead to unnecessary anxiety or treatments that compromise quality of life without assuring a longer life than a man ignorant of his condition would enjoy.
For most patients with localized tumors, surgical removal of the prostate gland (prostatectomy) is the initial treatment, despite possible side effects of urinary incontinence and impotence. Localized prostate cancer can often be cured. After surgery, a repeated blood test for protein-specific antigen can indicate whether any cancer remains. In metastatic disease, other treatments are employed depending on the stage of the disease and the age and health of the patient. Treatment options include external-beam radiation, implantation of radioactive isotopes, and palliative surgery. Hormonal manipulation by giving estrogens or other drugs, or by orchiectomy (removal of the testes), is sometimes used to decrease levels of testosterone. Very small cancers or slow-growing cancers in older men are sometimes watched, but not treated, without compromising life expectancy. Experimental treatments under investigation include cryosurgery, destroying the tumor by freezing.
See M. Korda, Man to Man (1996), and P. Walsh and J. F. Worthington, Dr. Patrick Walsh's Guide to Surviving Prostate Cancer (2001). See also publications of the National Cancer Institute and the American Cancer Society.
Lung cancers are classified according to the type of cell present in the tumor. The majority are referred to as non-small cell carcinomas. These include squamous cell or epidermoid carcinomas (the most common type worldwide), adenocarcinomas, and large cell carcinomas. Small cell carcinoma (which includes the subtypes oat cell and intermediate) comprises approximately 20% to 25% of lung cancers; it often has metastasized by the time it is detected. Lung cancer most commonly spreads to the brain, bone, liver, or bone marrow.
The primary symptoms of lung cancer are cough, shortness of breath, hoarseness, blood in the sputum, and pain. In some types, the cancer cells themselves produce hormones or other substances that can create an imbalance and result in various symptoms. Metastatic lung cancer also can cause symptoms that result from its effect on the organ to which the cancer has spread.
Diagnosis of lung cancer may be made by physical examination, chest X rays, bronchoscopy (see bronchoscope), or percutaneous needle biopsy (insertion of a fine needle through the skin and into the lung to obtain tissue for study). In many cases definitive diagnosis is made after surgical specimens have been evaluated. Evaluation of suspected sites of metastasis may involve CAT scans or magnetic resonance imaging (MRI). A special CAT-scanning technique (helical low-dose CAT-scanning) has also been used for initial diagnosis because it can detect small tumors before they have spread.
Lung cancer is staged according to its location, size, cell type, and spread. This staging plus the state of health of the patient are used to determine treatment.
Treatment typically consists of surgical excision of the tumor alone or in combination with either external-beam radiation therapy or chemotherapy using one or more anticancer drugs. Photodynamic therapy is sometimes used if the cancer is still localized. In this therapy a substance that makes cells more sensitive to light is injected into the body. When it has passed out of most of the tissues, but remains in the cancer cells, the cancer is destroyed by a beam of laser light.
Not starting to smoke or ceasing to smoke is by far the most effective lung cancer preventive. The risk of lung cancer in ex-smokers begins to decline about five years after quitting, and after 15 to 20 years their risk is 80% less than that of smokers. The reduction in cigarette smoking since the 1964 report of the Surgeon General's Advisory Committee on Health began to be translated into a decrease in the incidence of lung cancer in the 1990s; this decrease averaged more than 1% per year from 1990 to 1995. The preventive role of dietary antioxidants is under study.
See D. N. Carney, ed., Lung Cancer (1995). See also publications of the National Cancer Institute and the American Cancer Society.
Several genes that signal a hereditary predisposition to colon cancer have been identified. For example, mutations in either of two genes, MSH2 and MLH1, can predispose a person to hereditary nonpolyposis colorectal cancer (HNPCC). People in HNPCC families can undergo blood tests that can tell them whether they have an affected gene. With the information obtained from such screening, an appropriate course of preventive measures and follow-up tests can be initiated (see genetic screening).
A sudden change in bowel habits or blood in the feces (often detectable only in a laboratory) may be the first symptoms of colon cancer. In the early stages of the disease there may be no obvious symptoms. Diagnosis is made by physical examination of the rectum and a laboratory examination of blood for carcinoembryonic antigen (CEA), a tumor marker produced by colon cancers. These may be followed by an endoscopic examination of the colon with a sigmoidoscope (to examine the rectum and the adjoining sigmoid colon) or colonoscope (to examine the entire colon). A biopsy of any suspicious tissue, such as a polyp or a flat or depressed lesion, is then examined in a laboratory to determine if cancerous changes are present. If cancer is found, the patient is evaluated to determine the extent of the primary tumor and whether the disease has spread throughout the body.
Treatment depends upon the stage of the cancer. The initial treatment is usually local excision of the tumor or excision of a larger part of the colon followed by the joining of the two adjacent ends, a procedure referred to as end-to-end anastomosis. In some cases a colostomy (an opening that allows waste to be expelled through an opening in the abdomen rather than through the anus) is created either temporarily, to allow healing, or permanently, if significant portions of the colon have had to be removed. If the disease is advanced, radiation therapy, chemotherapy, or biological therapies (therapies that stimulate the body's own immune defenses against the disease) may be used in addition to surgery.
See publications of the National Cancer Institute, the American Cancer Society, and the United Ostomy Association.
Loss of contact inhibition accounts for two other characteristics of cancer cells: invasiveness of surrounding tissues, and metastasis, or spreading via the lymph system or blood to other tissues and organs. Whereas normal cells have a limited lifespan controlled by the telomere gene, which signals the end of the cell line, cancer cells contain telomerase, an enzyme that alters the telomere gene and allows the cell to continue to divide. Cancer tissue, growing without limits, competes with normal tissue for nutrients, eventually killing normal cells by nutritional deprivation. Cancerous tissue can also cause secondary effects, in which the expanding malignant growth puts pressure on surrounding tissue or organs or the cancer cells metastasize and invade other organs.
Virtually all organs and tissues are susceptible to cancer. Cancers are usually named for their site of origin. Cancer cells that spread to other organs are similar to those of the original tumor, therefore these secondary (metastatic) cancers are still named for their primary site even though they may have invaded a different organ. For example, lung cancer that has spread to the brain is called metastatic lung cancer, rather than brain cancer. Carcinoma in situ refers to a cancer that has not spread. (See neoplasm for more on cancer nomenclature.)
Cancer is the second leading cause of death in the United States. Lung cancer is the leading cause of cancer death in adults; leukemia is the most common cancer in children. Other common types of cancer include breast cancer (in women), prostate cancer (in men), and colon cancer (see also Hodgkin's disease). The incidence of particular cancers varies around the world and sometimes according to ethnic group. For instance, African Americans have comparatively higher cancer rates and cancer mortality rates. It is unclear whether this is due to differences in exposure or to biological susceptibility. The number of diagnosed cases of cancer rose steadily in the United States for decades, but in 1998 it was announced that the number of new cases had begun to decline.
Cancer results from mutations of certain genes that allow the cells to begin their uncontrolled growth. These mutations are either inherited or acquired. Acquired mutations are caused by repeated insults from triggers (e.g., cigarette smoke or ultraviolet rays) referred to as carcinogens. There is usually a latency period of years or decades between exposure to a carcinogen and the appearance of cancer. This, combined with the individual nature of susceptibility to cancer, makes it very difficult to establish a cause for many cancers.
The most significant avoidable carcinogens are the chemical components of tobacco smoke (see smoking). Dietary components, like excessive consumption of alcohol or of foods high in fat and low in fiber rather than fruits and vegetables that contain antioxidants and necessary micronutrients, have also been linked with various cancers. Some cancers may be triggered by hormone imbalances. For example, some daughters of mothers who had been given DES (diethylstilbestrol) during pregnancy to prevent miscarriage developed vaginal adenocarcinomas as young women. Aflatoxins are natural mold byproducts that can cause cancer of the liver.
Certain carcinogens present occupational hazards. For example, in the asbestos industry, workers have a high probability of developing lung and colon cancer or a particularly virulent cancer of the mesothelium (the lining of the chest and abdomen). Benzene and vinyl chloride are other known industrial carcinogens.
X rays and radioactive elements are also carcinogenic; the high incidence of leukemia and other cancers in Japanese survivors of the atomic bombing of Hiroshima and Nagasaki and the increased incidence of thyroid cancer after the Chernobyl nuclear disaster give evidence of this. Exposure to the ultraviolet radiation of sunlight is the leading cause of skin cancer.
Many other substances have been identified as carcinogenic to a greater or lesser extent, including chemicals in pesticides that leave residues on foods. The Delaney clause, an amendment (1958) to the U.S. Food, Drug, and Cosmetic Act that prohibits even minuscule amounts of carcinogens in the food supply, has provided the impetus for the investigation of many such chemicals but has also been a source of controversy between industry and environmentalists.
In the early 20th cent., the American virologist Peyton Rous showed that certain sarcomas affecting fowl could be transmitted by injection of an agent invisible under the microscope and later indentified as an RNA-containing virus. Other research uncovered oncogenic, or tumor-causing, viruses, first in experimental animals and then in humans. The Epstein-Barr virus, a member of the herpesvirus group, has been linked with a number of human cancers, including the lymphomas that often occur in immunosuppressed people, such as people with AIDS. Several human papillomaviruses (HPV) have also been shown to initiate cancers. For example, some types of HPV cause genital warts known as condylomata acuminata, which can lead to invasive cancer of the cervix, vulva, vagina, or penis, and another human papillomavirus has been associated with some forms of Kaposi's sarcoma. In addition, hepatitis B has been shown to increase the risk of liver cancer. Bacteria have also been associated with cancer. For example, the Helicobacter pylori bacterium that causes many ulcers is also associated with an increased risk of stomach cancer.
Risk to humans from carcinogens depends upon the dose and a person's biologic susceptibility. Factors influencing a person's biological susceptibility to cancer include age, sex, immune status, nutritional status, genetics, and ethnicity. Only 5% of all cancers in the United States are thought to be explained by inherited genetic mutations. Known genes associated with hereditary cancer include the aberrant BRCA1 and BRCA2 genes that increase breast cancer risk and the HNPCC gene that is linked with colon cancer. In hereditary forms, it is often the normal gene of the allele that is injured or destroyed, leaving the abnormal inherited gene in control. Nonhereditary cancers sometimes involve the same gene mutations that hereditary forms have.
Most bodily insults by carcinogens come to nothing because DNA has built-in repair mechanisms, but repeated insults can eventually result in mutations or altered gene expression in key genes called oncogenes and tumor-suppressor genes. Oncogenes produce growth factors, substances that signal a cell to grow and divide into daughter cells; tumor-suppressor genes (such as the p16, p53, and BRCA1 genes) normally produce a negative growth factor that tells a cell when to stop dividing. The abnormally inactivated tumor-suppressor gene or the abnormally activated oncogene is inherited by each of the cell's daughter cells, and a tumor develops. In many cases tumors remain small and in one place (in situ) for years, but some develop their own blood vessels (a process known as angiogenesis) and begin to grow and spread.
The classic symptoms of cancer are rapid weight loss; a change in a wart or mole; a sore that does not heal; difficulty swallowing; chronic hoarseness, blood in phlegm, urine, or stool (a consequence of angiogenesis); chronic abdominal pain; a change in size or shape of the testes; a change in bowel habits; a lump in the breast; and unusual vaginal bleeding. Many of these and other symptoms are often nonspecific, e.g., weakness, loss of appetite, and weight loss, and thus are not obvious in the early stages. Sometimes the side effects of tumor growth are more severe than the actual effects of the malignancy; for example, some tumors secrete materials such as serotonin and histamine that can cause drastic vascular changes. Conversely, cancers that destroy tissue may also have serious effects, e.g., malignant destruction of bone tissue may raise the blood level of calcium.
As more has been learned about cancer, emphasis on prevention and early detection has increased. Cessation of smoking and other tobacco use is the most important controllable means of prevention; smoking causes about 30% of the cancer deaths in the United States. A diet low in fat and high in fiber, including a variety of fruits and vegetables (especially those high in antioxidants), is also recommended. Effective protection against the rays of the sun is recommended to avoid skin cancer. Another preventive approach is vaccination against cancer-causing viruses, such as the hepatitis B virus.
Cancers caught early, before metastasis, have the best cure rates. A number of screening tools are now available to allow early detection and treatment. Among these are monthly breast self-examinations and regular mammography and Pap tests for women, regular self-examination of the testes for young men, and, for older men, regular examination of the prostate gland with blood tests for prostate-specific antigen (PSA) tumor marker (a substance in the body that heralds an increased cancer risk). Colonoscopy plus physical examination and laboratory tests for carcinoembryonic antigen (CEA) are recommended for detection of colon cancer. Self-examination of the skin is important for the early detection of skin cancers. Suspicion of a tumor may be confirmed by X-ray study, endoscopy (see endoscope), blood tests for various tumor markers, and biopsy from which the cells are examined by a pathologist for malignancy.
Developments in the treatment of cancer have led to greatly improved survival and quality of life for cancer patients in the past three decades. Traditionally, cancer has been treated by surgery, chemotherapy, and radiation therapy. In recent years immunotherapy has been added to that list. New drugs and techniques are constantly being researched and developed, such as antiangiogenic agents (e.g., angiostatin and endostatin), genetically engineered monoclonal antibodies, retinoid agents, and vaccine agents (stimulating the immune system).
For most kinds of cancer, surgery remains the primary treatment. It is most effective if the cancer is caught while still localized. Some cancers that spread to the lymph system are sometimes treated by extensive surgical removal of tissue, but the trend is toward more conservative procedures (see mastectomy). Cryosurgery, the use of extreme cold, and electrodessication, the use of extreme heat, are also being used to kill cancerous tissue and the surrounding blood supply. If the cancer has metastasized, surgery is often replaced by or followed by radiation therapy (which is a localized therapy) and chemotherapy (which is a system-wide therapy).
For some cancers, radiation therapy—either from an external beam or from implanted radioactive pellets—is the primary treatment. The usual forms are X rays and gamma rays. Use of radioactive elements specific for particular target organs, such as radioactive iodine specific for the thyroid gland, is effective in treating malignancies of those organs.
Cytotoxic chemotherapy is used as a primary treatment for some cancers, such as lymphomas and leukemias or as an addition to surgery or radiation therapy. Cytotoxic drugs (drugs that are toxic to cells) are aimed at rapidly proliferating cells and interfere with nucleic acid and protein synthesis in the cancer cell, but they are often toxic to normal rapidly proliferating cells, such as bone marrow and hair cells. Often a combination of cytotoxic drugs is used. Drugs that reduce side effects may be added to the treatment, such as antinausea agents.
Hormonal chemotherapy is based upon the fact that the growth of some malignant tumors (specifically those of the reproductive organs) is influenced by reproductive hormones. Tamoxifen is a naturally occurring estrogen inhibitor used to prevent breast cancer recurrences. Flutamide is sometimes used in prostate cancer to inhibit androgen uptake. Sex-hormone related drugs such as DES and tamoxifen, which may be carcinogenic under some conditions, have proven to be protective under others.
More specifically targeted drug therapies have begun to be explored as a better understanding of the molecular biology of individual cancers has been developed. Such drugs are designed to kill only cancer cells while having fewer side effects. Gleevec (STI-571), which is used to treat chronic myelogenous leukemia and some other cancers, inhibits certain kinase receptors that become hyperactive in cancer cells, resulting in the cells' rapid reproduction.
Immunotherapy (sometimes called biological therapy) uses substances that help the body mobilize its immune defenses. Some attack the tumor itself, while others bolster the body's ability to withstand conventional chemotherapy treatment. Other new or experimental therapies include drugs that inhibit angiogenesis and photodynamic therapy, in which a patient is given a drug to make the tumor light-sensitive, after which the tumor is exposed to bright laser light. The best choice of treatment will increasingly be influenced by the growing field of molecular pathology, in which characteristics of individual cancers (e.g., virulence or resistance to a particular treatment) can be revealed by analysis of their genetic characteristics rather than by the microscope.
Besides treatment of the cancer itself, progress has been made in the management of the chronic pain that often accompanies cancer and in the education of patients and physicians in such techniques as biofeedback, acupuncture, and meditation and the appropriate use of narcotics and other medications. Because of improvements in early detection and treatment, many more people are now living with cancer. Over half of all people with cancer now survive for five or more years.
See S. S. Lang and R. B. Patt, You Don't Have to Suffer (1994); P. Greenwald et al., Cancer Prevention and Control (1995); M. Dollinger et al., Everyone's Guide to Cancer Therapy (3d ed. 1997); C. N. Coleman, Understanding Cancer (1998). See also publications of the National Cancer Institute and the American Cancer Society.
Loss of contact inhibition accounts for two other characteristics of cancer cells: invasiveness of surrounding tissues, and metastasis, or spreading via the lymph system or blood to other tissues and organs. Whereas normal cells have a limited lifespan controlled by the telomere gene, which signals the end of the cell line, cancer cells contain telomerase, an enzyme that alters the telomere gene and allows the cell to continue to divide. Cancer tissue, growing without limits, competes with normal tissue for nutrients, eventually killing normal cells by nutritional deprivation. Cancerous tissue can also cause secondary effects, in which the expanding malignant growth puts pressure on surrounding tissue or organs or the cancer cells metastasize and invade other organs.
Virtually all organs and tissues are susceptible to cancer. Cancers are usually named for their site of origin. Cancer cells that spread to other organs are similar to those of the original tumor, therefore these secondary (metastatic) cancers are still named for their primary site even though they may have invaded a different organ. For example, lung cancer that has spread to the brain is called metastatic lung cancer, rather than brain cancer. Carcinoma in situ refers to a cancer that has not spread. (See neoplasm for more on cancer nomenclature.)
Cancer is the second leading cause of death in the United States. Lung cancer is the leading cause of cancer death in adults; leukemia is the most common cancer in children. Other common types of cancer include breast cancer (in women), prostate cancer (in men), and colon cancer (see also Hodgkin's disease). The incidence of particular cancers varies around the world and sometimes according to ethnic group. For instance, African Americans have comparatively higher cancer rates and cancer mortality rates. It is unclear whether this is due to differences in exposure or to biological susceptibility. The number of diagnosed cases of cancer rose steadily in the United States for decades, but in 1998 it was announced that the number of new cases had begun to decline.
Cancer results from mutations of certain genes that allow the cells to begin their uncontrolled growth. These mutations are either inherited or acquired. Acquired mutations are caused by repeated insults from triggers (e.g., cigarette smoke or ultraviolet rays) referred to as carcinogens. There is usually a latency period of years or decades between exposure to a carcinogen and the appearance of cancer. This, combined with the individual nature of susceptibility to cancer, makes it very difficult to establish a cause for many cancers.
The most significant avoidable carcinogens are the chemical components of tobacco smoke (see smoking). Dietary components, like excessive consumption of alcohol or of foods high in fat and low in fiber rather than fruits and vegetables that contain antioxidants and necessary micronutrients, have also been linked with various cancers. Some cancers may be triggered by hormone imbalances. For example, some daughters of mothers who had been given DES (diethylstilbestrol) during pregnancy to prevent miscarriage developed vaginal adenocarcinomas as young women. Aflatoxins are natural mold byproducts that can cause cancer of the liver.
Certain carcinogens present occupational hazards. For example, in the asbestos industry, workers have a high probability of developing lung and colon cancer or a particularly virulent cancer of the mesothelium (the lining of the chest and abdomen). Benzene and vinyl chloride are other known industrial carcinogens.
X rays and radioactive elements are also carcinogenic; the high incidence of leukemia and other cancers in Japanese survivors of the atomic bombing of Hiroshima and Nagasaki and the increased incidence of thyroid cancer after the Chernobyl nuclear disaster give evidence of this. Exposure to the ultraviolet radiation of sunlight is the leading cause of skin cancer.
Many other substances have been identified as carcinogenic to a greater or lesser extent, including chemicals in pesticides that leave residues on foods. The Delaney clause, an amendment (1958) to the U.S. Food, Drug, and Cosmetic Act that prohibits even minuscule amounts of carcinogens in the food supply, has provided the impetus for the investigation of many such chemicals but has also been a source of controversy between industry and environmentalists.
In the early 20th cent., the American virologist Peyton Rous showed that certain sarcomas affecting fowl could be transmitted by injection of an agent invisible under the microscope and later indentified as an RNA-containing virus. Other research uncovered oncogenic, or tumor-causing, viruses, first in experimental animals and then in humans. The Epstein-Barr virus, a member of the herpesvirus group, has been linked with a number of human cancers, including the lymphomas that often occur in immunosuppressed people, such as people with AIDS. Several human papillomaviruses (HPV) have also been shown to initiate cancers. For example, some types of HPV cause genital warts known as condylomata acuminata, which can lead to invasive cancer of the cervix, vulva, vagina, or penis, and another human papillomavirus has been associated with some forms of Kaposi's sarcoma. In addition, hepatitis B has been shown to increase the risk of liver cancer. Bacteria have also been associated with cancer. For example, the Helicobacter pylori bacterium that causes many ulcers is also associated with an increased risk of stomach cancer.
Risk to humans from carcinogens depends upon the dose and a person's biologic susceptibility. Factors influencing a person's biological susceptibility to cancer include age, sex, immune status, nutritional status, genetics, and ethnicity. Only 5% of all cancers in the United States are thought to be explained by inherited genetic mutations. Known genes associated with hereditary cancer include the aberrant BRCA1 and BRCA2 genes that increase breast cancer risk and the HNPCC gene that is linked with colon cancer. In hereditary forms, it is often the normal gene of the allele that is injured or destroyed, leaving the abnormal inherited gene in control. Nonhereditary cancers sometimes involve the same gene mutations that hereditary forms have.
Most bodily insults by carcinogens come to nothing because DNA has built-in repair mechanisms, but repeated insults can eventually result in mutations or altered gene expression in key genes called oncogenes and tumor-suppressor genes. Oncogenes produce growth factors, substances that signal a cell to grow and divide into daughter cells; tumor-suppressor genes (such as the p16, p53, and BRCA1 genes) normally produce a negative growth factor that tells a cell when to stop dividing. The abnormally inactivated tumor-suppressor gene or the abnormally activated oncogene is inherited by each of the cell's daughter cells, and a tumor develops. In many cases tumors remain small and in one place (in situ) for years, but some develop their own blood vessels (a process known as angiogenesis) and begin to grow and spread.
The classic symptoms of cancer are rapid weight loss; a change in a wart or mole; a sore that does not heal; difficulty swallowing; chronic hoarseness, blood in phlegm, urine, or stool (a consequence of angiogenesis); chronic abdominal pain; a change in size or shape of the testes; a change in bowel habits; a lump in the breast; and unusual vaginal bleeding. Many of these and other symptoms are often nonspecific, e.g., weakness, loss of appetite, and weight loss, and thus are not obvious in the early stages. Sometimes the side effects of tumor growth are more severe than the actual effects of the malignancy; for example, some tumors secrete materials such as serotonin and histamine that can cause drastic vascular changes. Conversely, cancers that destroy tissue may also have serious effects, e.g., malignant destruction of bone tissue may raise the blood level of calcium.
As more has been learned about cancer, emphasis on prevention and early detection has increased. Cessation of smoking and other tobacco use is the most important controllable means of prevention; smoking causes about 30% of the cancer deaths in the United States. A diet low in fat and high in fiber, including a variety of fruits and vegetables (especially those high in antioxidants), is also recommended. Effective protection against the rays of the sun is recommended to avoid skin cancer. Another preventive approach is vaccination against cancer-causing viruses, such as the hepatitis B virus.
Cancers caught early, before metastasis, have the best cure rates. A number of screening tools are now available to allow early detection and treatment. Among these are monthly breast self-examinations and regular mammography and Pap tests for women, regular self-examination of the testes for young men, and, for older men, regular examination of the prostate gland with blood tests for prostate-specific antigen (PSA) tumor marker (a substance in the body that heralds an increased cancer risk). Colonoscopy plus physical examination and laboratory tests for carcinoembryonic antigen (CEA) are recommended for detection of colon cancer. Self-examination of the skin is important for the early detection of skin cancers. Suspicion of a tumor may be confirmed by X-ray study, endoscopy (see endoscope), blood tests for various tumor markers, and biopsy from which the cells are examined by a pathologist for malignancy.
Developments in the treatment of cancer have led to greatly improved survival and quality of life for cancer patients in the past three decades. Traditionally, cancer has been treated by surgery, chemotherapy, and radiation therapy. In recent years immunotherapy has been added to that list. New drugs and techniques are constantly being researched and developed, such as antiangiogenic agents (e.g., angiostatin and endostatin), genetically engineered monoclonal antibodies, retinoid agents, and vaccine agents (stimulating the immune system).
For most kinds of cancer, surgery remains the primary treatment. It is most effective if the cancer is caught while still localized. Some cancers that spread to the lymph system are sometimes treated by extensive surgical removal of tissue, but the trend is toward more conservative procedures (see mastectomy). Cryosurgery, the use of extreme cold, and electrodessication, the use of extreme heat, are also being used to kill cancerous tissue and the surrounding blood supply. If the cancer has metastasized, surgery is often replaced by or followed by radiation therapy (which is a localized therapy) and chemotherapy (which is a system-wide therapy).
For some cancers, radiation therapy—either from an external beam or from implanted radioactive pellets—is the primary treatment. The usual forms are X rays and gamma rays. Use of radioactive elements specific for particular target organs, such as radioactive iodine specific for the thyroid gland, is effective in treating malignancies of those organs.
Cytotoxic chemotherapy is used as a primary treatment for some cancers, such as lymphomas and leukemias or as an addition to surgery or radiation therapy. Cytotoxic drugs (drugs that are toxic to cells) are aimed at rapidly proliferating cells and interfere with nucleic acid and protein synthesis in the cancer cell, but they are often toxic to normal rapidly proliferating cells, such as bone marrow and hair cells. Often a combination of cytotoxic drugs is used. Drugs that reduce side effects may be added to the treatment, such as antinausea agents.
Hormonal chemotherapy is based upon the fact that the growth of some malignant tumors (specifically those of the reproductive organs) is influenced by reproductive hormones. Tamoxifen is a naturally occurring estrogen inhibitor used to prevent breast cancer recurrences. Flutamide is sometimes used in prostate cancer to inhibit androgen uptake. Sex-hormone related drugs such as DES and tamoxifen, which may be carcinogenic under some conditions, have proven to be protective under others.
More specifically targeted drug therapies have begun to be explored as a better understanding of the molecular biology of individual cancers has been developed. Such drugs are designed to kill only cancer cells while having fewer side effects. Gleevec (STI-571), which is used to treat chronic myelogenous leukemia and some other cancers, inhibits certain kinase receptors that become hyperactive in cancer cells, resulting in the cells' rapid reproduction.
Immunotherapy (sometimes called biological therapy) uses substances that help the body mobilize its immune defenses. Some attack the tumor itself, while others bolster the body's ability to withstand conventional chemotherapy treatment. Other new or experimental therapies include drugs that inhibit angiogenesis and photodynamic therapy, in which a patient is given a drug to make the tumor light-sensitive, after which the tumor is exposed to bright laser light. The best choice of treatment will increasingly be influenced by the growing field of molecular pathology, in which characteristics of individual cancers (e.g., virulence or resistance to a particular treatment) can be revealed by analysis of their genetic characteristics rather than by the microscope.
Besides treatment of the cancer itself, progress has been made in the management of the chronic pain that often accompanies cancer and in the education of patients and physicians in such techniques as biofeedback, acupuncture, and meditation and the appropriate use of narcotics and other medications. Because of improvements in early detection and treatment, many more people are now living with cancer. Over half of all people with cancer now survive for five or more years.
See S. S. Lang and R. B. Patt, You Don't Have to Suffer (1994); P. Greenwald et al., Cancer Prevention and Control (1995); M. Dollinger et al., Everyone's Guide to Cancer Therapy (3d ed. 1997); C. N. Coleman, Understanding Cancer (1998). See also publications of the National Cancer Institute and the American Cancer Society.
Epidemiological study has identified certain risk factors that increase the possibility that a woman will get breast cancer, although not all women with breast cancer have these traits, and many women with all of these traits do not develop the disease. Risk factors include age (the incidence of breast cancer is rare in women under 35—most cases occur in women over 60); a history of breast cancer in a close blood relative; and a history of breast cancer or benign proliferative breast disease. A high cumulative exposure to female sex hormones (estrogen and progesterone) appears to increase the risk of some breast cancers. Hormonally related risk factors include early menarch (before age 12), late menopause (after age 55), having no children or postponing childbirth, and obesity in women over 50.
Many other possible associations are under study, such as those relating to postmenopausal estrogen replacement, alcohol and fat consumption, lack of exercise, and exposure to pesticides and other environmental chemicals. A 2002 report on the association of estrogen replacement therapy with an increased risk of breast cancer led to a large drop in prescriptions for the drugs used in such therapy; a coincident drop in the incidence of breast cancer tumors, especially estrogen-positive tumors, which apparently could not be accounted for by other causes, strongly suggested a link between the two. Tumors in women of African descent are known to be particularly aggressive.
Like all cancers, breast cancers result from changes in the structure or function of genes that are key to the regulation of cellular growth, differentiation, or repair. Acquired changes in a number of specific genes have been associated with the disease; these are changes that occur during a person's lifetime but are not inherited or passed on. About 5% of women with breast cancer have an inherited susceptibility to the disease, and most of these women have an inherited mutation in one of two genes. In 1994 it was discovered that women who inherit a mutated BRCA1 gene have an almost 85% chance of developing breast cancer and an increased chance of developing uterine cancer. BRCA1 normally acts to prevent tumors by repairing damage to the genetic material caused by oxidation, a chemical process that in the body occurs naturally during metabolism. Defective BRCA1 genes cannot repair this damage, allowing its effects to accumulate over time. Cells with oxidative damage to the genes that control their growth can proliferate, or become cancerous. The defective gene can be inherited from either parent, but appears to cause breast cancer only in women. Young women who get breast cancer often come from families that carry a BRCA1 mutation. BRCA1 mutations account for about half of known hereditary breast cancers. Another gene, named BRCA2, has also been identified. BRCA2 mutations have been associated with both female and rare male breast cancers. The two genes may also play a role in some ovarian cancers and sporadic (nonhereditary) breast cancer cases.
Monthly breast self-examination and regular mammography are the recommended methods of breast cancer early detection. The first sign of breast cancer may be a lump in the breast; a thickening, swelling, or dimpling; skin irritation or scaliness; pain; or a discharge or tenderness of the nipple. A biopsy can rule out or confirm a malignancy. A major recent study has shown that the drug tamoxifen can prevent breast cancer in women considered at high risk of developing the disease.
In most cases, treatment for breast cancer begins with surgical excision of the tumor. Modern treatment attempts to preserve as much tissue as possible for both functional and cosmetic reasons. This may mean a lumpectomy (simple excision of only the cancerous tumor) or mastectomy (excision of part or all of the breast tissue, sometimes with adjacent muscle). The lymph nodes under the arm are often excised in a procedure known as an axillary dissection. In some cases, chemotherapy and external beam radiation therapy or radioactive isotopes implanted directly into the area of the cancer, are used in addition to or instead of surgery. Hormone therapy in the form of ovary removal or a drug such as tamoxifen or anastrozole is sometimes used to slow the growth of or prevent recurrence of hormonally sensitive tumors. Bone marrow transplantation is sometimes used when bone marrow that has been destroyed by large doses of chemotherapy or radiation therapy needs to be replaced.
Many women who have had a mastectomy decide to have breast reconstruction surgery. This reconstruction is done with breast implants or the patient's own tissue. Due to the controversy over silicone implants, saline-filled implants were used from 1992 to 1998, but either type may be used now. Women who have had an axillary dissection often experience chronic, progressive pain, numbness, and weakness in the affected arm. Lymphedema, painful swelling of the arm, can occur after node dissection or radiation treatment of the lymph nodes. Following surgery, chemotherapy, and radiation, women who had estrogen-sensitive tumors are given tamoxifen or, if they are postmenopausal, anastrozole or another aromatase inihibitor to help prevent a recurrence.
See Y. Hirshaut and P. I. Pressman, Breast Cancer: The Complete Guide (3d ed. 2000). See also publications of the National Cancer Institute, the American Cancer Society, the National Breast Cancer Association, and the National Lymphedema Network.
Malignant tumour of the uterus. Cancers affecting the lining of the uterus (endometrium) are the most common cancers of the female reproductive tract. Risk factors include absence of pregnancy, early age of first menstruation (before age 12), late onset of menopause (after age 52), obesity, diabetes, and estrogen replacement therapy. Additional risk factors are a personal history of breast or ovarian cancer, age (over age 40), and a family history of uterine cancer. Whites are more likely to develop uterine cancer than are blacks. The major symptom is vaginal bleeding or discharge. Treatment may begin with simple or radical hysterectomy. Some uterine cancers are treated in part by hormonal therapy, radiation therapy, or chemotherapy.
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Malignant tumour of the testis, or testicle. Although relatively rare, testicular cancer is the most common malignancy for men between the ages of 20 and 34. It typically affects men between 15 and 39 years old. A developmental abnormality of males in which one or both testes fail to descend into the scrotum about the time of birth increases the risk of developing the cancer later in life. The most notable symptom of testicular cancer is the formation of a painless lump in either testis. Treatment usually consists of the surgical removal of the cancerous testis, followed by radiation therapy or chemotherapy if the cancer has metastasized.
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Malignant tumour of the stomach. The main risk factors include a diet high in salted, smoked, or pickled foods; Helicobacter pylori infection; tobacco and alcohol use; age (over age 60); and a family history of stomach cancer. Males develop stomach cancer at approximately twice the rate of females. Symptoms may be abdominal pain or swelling, unexplained weight loss, vomiting, and poor digestion. Surgery is the only method for treating stomach cancer, although radiation therapy or chemotherapy may be used in conjunction with surgery or to relieve symptoms.
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Malignant tumour of the skin, including some of the most common human cancers. Though recognizable at an early stage, it has a significant death rate. Light-skinned people have the highest risk but can reduce it by limiting exposure to sunlight and to ionizing radiation. The most common types arise in the epidermis (outer skin layer) and have become more frequent with the thinning of the atmosphere's ozone layer. The most serious form is melanoma, which is frequently fatal if not treated early with surgery. Cancers arising from the dermis are rare; the best-known is Kaposi sarcoma.
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Malignant tumour of the prostate gland. Prostate cancer commonly occurs in men over age 50. Symptoms include frequent or painful urination, blood in the urine, sexual dysfunction, swollen lymph nodes in the groin, and pain in the pelvis, hips, back, or ribs. The likelihood of developing prostate cancer doubles if there is a family history. Treatment may include surgery, radiation therapy, hormone therapy, chemotherapy, or a combination of two or more of these approaches.
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Malignant tumour of the pancreas. Risk factors include smoking, a diet high in fat, exposure to certain industrial products, and diseases such as diabetes and chronic pancreatitis. Pancreatic cancer is more common in men. Symptoms often do not appear until pancreatic cancer is advanced; they include abdominal pain, unexplained weight loss, and difficulty digesting fatty foods. Surgery, radiation therapy, chemotherapy, or some combination of these may be used to treat the disease.
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Malignant tumour of the ovaries. Risk factors include early age of first menstruation (before age 12), late onset of menopause (after age 52), absence of pregnancy, presence of specific genetic mutations, use of fertility drugs, and personal history of breast cancer. Symptoms such as abdominal swelling, pelvic pressure or pain, and unusual vaginal bleeding often do not appear until ovarian cancer is advanced. Surgery, sometimes followed by chemotherapy or radiation therapy, is an effective treatment for most ovarian cancers.
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Malignant tumour of the lung. Four major types (squamous-cell carcinoma, adenocarcinoma, large-cell carcinoma, and small-cell carcinoma) have roughly equal prevalence. Most cases are due to long-term cigarette smoking. Heavy smoking and starting smoking earlier in life increase the risk. Passive inhalation (“secondhand smoke”) is linked to lung cancer in nonsmokers. Other risk factors include exposure to radon or asbestos. Symptoms, including coughing (sometimes with blood), chest pain, and shortness of breath, seldom appear until lung cancer is advanced, when treatment with surgery, chemotherapy, and radiation or some combination of the three is less effective. Most patients die within a year of diagnosis.
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Malignant tumour of the larynx. The larynx is affected by both benign and malignant tumours. Squamous-cell carcinoma, the most common laryngeal malignancy, is associated with smoking and alcohol consumption; it is more common in men. Prolonged hoarseness without pain is the major symptom and should always be investigated. Radiation therapy or surgery may be used to treat tumours.
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Malignant tumour of the large intestine (colon) or rectum. Risk factors include age (after age 50), family history of colorectal cancer, chronic inflammatory bowel diseases, benign polyps, physical inactivity, and a diet high in fat. Many of the symptoms are associated with abnormal digestion and elimination. Colorectal cancer is treated by surgery, chemotherapy, or radiation therapy.
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Uncontrolled multiplication of abnormal cells. Cancerous cells and tissues have abnormal growth rates, shapes, sizes, and functioning. Cancer may progress in stages from a localized tumour (confined to the site of origin) to direct extension (spread into nearby tissue or lymph nodes) and metastasis (spread to more distant sites via the blood or lymphatic system). This malignant growth pattern distinguishes cancerous tumours from benign ones. Cancer is also classified by grade, the extent to which cell characteristics remain specific to their tissue of origin. Both stage and grade affect the chances of survival. Genetic factors and immune status affect susceptibility. Triggers include hormones, viruses, smoking, diet, and radiation. Cancer can begin in almost any tissue, including blood (see leukemia) and lymph (see lymphoma). When it metastasizes, it remains a cancer of its tissue of origin. Early diagnosis and treatment increase the chance of cure. Treatment may include chemotherapy, surgery, and radiation therapy. Seealso bladder cancer; breast cancer; carcinogen; colorectal cancer; Kaposi sarcoma; laryngeal cancer; lung cancer; ovarian cancer; pancreatic cancer; prostate cancer; skin cancer; stomach cancer; uterine cancer.
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Malignant tumour in a breast, usually in women after menopause. Risk factors include family history of breast cancer, prolonged menstruation, late first pregnancy (after age 30), obesity, alcohol use, and some benign tumours. Most breast cancers are adenocarcinomas. Any lump in the breast needs investigation because it may be cancer. Treatment may begin with radical or modified mastectomy or lumpectomy (in which only the tumour is removed), followed by radiation therapy, chemotherapy, or removal of the ovaries or adrenal glands.
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Malignant tumour of the bladder. The most significant risk factor associated with bladder cancer is smoking. Exposure to chemicals called arylamines, which are used in the leather, rubber, printing, and textiles industries, is another risk factor. Most bladder cancers are diagnosed after the age of 60; men are affected more than women. Symptoms include blood in the urine, difficulty urinating, excessive urination, or, more rarely, painful urination. Bladder cancer can be treated with surgery, radiation therapy, or chemotherapy.
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Parallel of latitude approximately 23°27' north of the terrestrial Equator. It is the northern boundary of the tropics and marks the northernmost latitude at which the Sun can be seen directly overhead at noon.
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(Latin: “Crab”) In astronomy, the constellation lying between Leo and Gemini; in astrology, the fourth sign of the zodiac, governing approximately the period June 22–July 22. It is represented as a crab (or crayfish), a reference to the crab in Greek mythology that pinched Heracles while he was fighting the Lernaean hydra. Heracles crushed the crab, but his enemy Hera rewarded it by placing it in the sky as a constellation.
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