cancer

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The common name for a malignant neoplasm or tumor. Neoplasms are new growths and can be divided into benign and malignant types, although in some instances the distinction is unclear. The most important differentiating feature is that a malignant tumor will invade surrounding structures and metastasize (spread) to distant sites whereas a benign tumor will not. Other distinctions between benign and malignant growth include the following: malignancies but not benign types are composed of highly atypical cells; malignancies tend to show more rapid growth than benign neoplasms, and are composed, in part, of cells showing frequent mitotic activity; and malignant tumors tend to grow progressively without self-limitation. See also Mitosis; Tumor.

Malignant neoplasms that arise from cells of mesenchymal origin (for example, bone muscle, connective tissue) are called sarcomas. Those that develop from epithelial cells and tissues (for example, skin, mucosal membranes, and glandular tissues) are termed carcinomas. Carcinomas usually metastasize initially by way of lymphatic channels, whereas sarcomas spread to distant organs through the bloodstream.

The cause of most types of human cancers is unknown. However, a number of factors are thought to be operative in the development of some malignant neoplasms. Genetic factors are thought to be causally related to some human malignancies such as lung cancer in that the incidence of cancer among persons with a positive family history of cancer may be three times as high as in those who do not have a family history. A number of different neoplasms are known to be genetically related and may be due to damage or changes in chromosome structure. Radiation in various forms is thought to be responsible for up to 3% of all cancers. In the United States the carcinogens in tobacco account for up to one-third of all cancer deaths in men and 5–10% in women. The increasing incidence and death rate from cancer of the lung in women is alarming, and is directly related to the increasing prevalence of cigarette smoking by women. Cigarette smoking and the heavy consumption of ethyl alcohol appear to act synergistically in the development of oral, esophageal, and gastric cancers. There are several carcinogens to which people are exposed occupationally that result in the development of cancer, although the mechanisms by which they cause neoplasms are sometimes poorly understood. For example, arsenic is associated with lung, skin, and liver cancer and asbestos causes mesotheliomas (cancer of the pleural, peritoneal, and pericardial cavities). Certain drugs and hormones have been found to cause certain types of neoplasms. Postmenopausal women taking estrogen hormones have a much higher incidence of endometrial cancer (cancer of the lining of the uterine cavity). The role of diet and nutrition in the development of malignant tumors is controversial and still under investigation. Some epidemiologic studies have shown that certain diets, such as those high in saturated fats, are associated with an increased incidence of certain types of neoplasm, such as colon cancer. The role of viruses in the development of human cancers is being studied. See also Mutagens and carcinogens; Radiation biology; Tumor viruses.

It is generally accepted that the neoplastic condition is caused by alterations in genetic mechanisms involved in cellular differentiation. In malignant cells, normal cellular processes are bypassed due to the actions of a select group of genes called oncogenes which regulate cellular activities. A group of these highly conserved genes exist in normal cells and are called proto-oncogenes. These genes appear to be important in regulating cellular growth during embryonic development. It is thought that in carcinogenesis these proto-oncogenes become unmasked or changed during the breakage or translocation of chromosomes. These genes that were previously suppressed in the cell then become functional, and in some instances lead to the excessive production of growth factors which could be important in the neoplastic state. See also Oncogenes.

The physical changes that cancer produces in the body vary considerably, depending on the type of tumor, location, rate of growth, and whether it has metastasized. The American Cancer Society has widely publicized cancer's seven warning signals: (1) a change in bowel or bladder habits; (2) a sore that does not heal; (3) unusual bleeding or discharge; (4) a thickening or lump in the breast or elsewhere; (5) indigestion or difficulty in swallowing; (6) an obvious change in a wart or mole; and (7) a nagging cough or hoarseness. In current medical practice, most cancers are staged according to tumor size, metastases to lymph nodes, and distant metastases. This type of staging is useful in determining the most effective therapy and the prognosis.

The progression, or lack thereof, of a given cancer is highly variable and depends on the type of neoplasm and the response to treatment. Treatment modalities include surgery, chemotherapy, radiation therapy, hormonal manipulation, and immunotherapy. In general, each type of cancer is treated very specifically, and often a combination of the various modalities is used, for example, surgery preceded or followed by radiation therapy. The response to treatment depends on the type of tumor, its size, and whether it has spread. See also Chemotherapy; Immunotherapy; Oncology; Radiography.

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A wide variety of diseases characterized by uncontrolled growth of tissue. Dietary factors may be involved in the initiation of some forms of cancer, and a high-fat diet has been especially implicated. There is some evidence that antioxidant nutrients such as carotene, vitamins C and E, and the mineral selenium may be protective. See also carcinogen.

Patients with advanced cancer are frequently malnourished, the condition of cachexia.

A group of diseases characterized by the uncontrolled growth of abnormal cells which have the ability to spread throughout the body or body parts. Cancers are among the most insidious and feared diseases. There have been great advances in our understanding of cancers in recent years, but much remains unknown. Nevertheless, cancer research is a very active field and new knowledge is gained every day enabling doctors to establish the causes for the diseases and design new treatments. Unfortunately, a lot of this is pioneering research and sometimes claims are made prematurely or are exaggerated.

Diet has featured strongly in cancer research. Results are often inconclusive, but there are clear indications that some diets can affect the risk of contracting cancer. Scotland has a diet with one of the lowest levels of fruit and vegetable consumption in the world, and a particularly high incidence of bowel cancer. Some doctors believe that up to 1563 deaths a year, 90 per cent of the total caused by bowel cancer, could be avoided if people changed their diet. It is believed that high fibre diets with plenty of fruit and vegetables give some (but not complete) protection against bowel cancer, and a substance in garlic (diallylsulphide) may reduce the risk of stomach cancers. Animal research has shown that certain fish oil derivatives may halt the growth of some tumours. It is claimed that gammalinoleic acid (GLA), found in evening primrose oil, has powerful anti-cancer properties; and there is a catalogue of claims about the effects of antioxidants, with the vitamins A, C, and E gaining most attention recently. Cancers of the pancreas, prostate, bladder, breast, cervix, womb, ovary, small intestine, and rectum have at some time been linked with obesity and unhealthy diets. These are just a few examples of the possible relationship between foods and cancers, and it is important to emphasize that many of the claims are not fully substantiated. In January 1993 the European Prospective Investigation of Cancer was set up to examine links between diet and cancer. Detailed diet diaries and health records of 250 000 people across Europe are being studied over a ten-year period. The results will allow researchers to examine the diets of apparently healthy patients who later develop cancer.

The relationship between exercise and cancers has been studied in less depth. The general consensus, although tentative, seems to be that there is an optimum amount of exercise that activates the immune system and reduces risk of tumour development; regular exercise above and below this level may weaken the immune system and increase the risk of certain cancers. One study undertaken in 1977 examined the exercise habits of 17 000 Harvard graduates. Those who burned at least 1000 extra Calories a week exercising had half the incidence of colon cancer compared with sedentary people within the same age group. It was suggested that exercise may reduce the intestinal transit time (the amount of time food remains in the gut) and the exposure of the gut wall to carcinogens. The results, however, may be due to differences in diet between exercisers and non-exercisers.

The term ‘cancer’ refers to a diverse group of diseases, characterized by uncontrolled growth of cells, leading to a variety of pathological consequences and frequently death. It is typically a disease of the elderly — the incidence of all forms of cancer increases markedly with age. However, it also occurs occasionally in children. Often the abnormal cell growth results in the establishment of a macroscopic lump or tumour ‘oncos’ in Greek, hence the term ‘oncology’ for the study of cancer), which may grow to a large size and kill the patient by a local effect, e.g. occlusion of vital ducts — even the alimentary tract — or by compromising the functioning of some distant organ. Indeed, the very word ‘cancer’ derives from the appearance of solid tumours as noted on post mortem examination by early physicians, who likened their appearance to that of a crab (Cancer) because of the irregular and disorganized appearance of the threads of the tumour radiating from a central body. Some forms of cancer, however, do not grow as coherent lumps but as individual cells diffused through the vascular system; these diseases — leukaemias and lymphomas — are associated with quite a different pathological profile.

Not all tumours of the human body are cancerous, however. Everyone is familiar with the common wart, and probably other skin lesions that result from local proliferation of cells, and which are quite benign. What distinguishes cancerous tumours and renders them seriously life-threatening is the property of malignancy, which derives from the capacity of the cells to invade surrounding tissue and to break off from the parent lump, migrate around the body in the blood vessels or the lymphatic system, and set up secondary foci of cancerous growth at distant sites. It is the latter phenomenon, metastatic spread of the disease, which most frequently kills cancer patients. The secondary foci — metastases — often occur in the brain, lungs, or liver, because these organs have a large blood supply and a well-developed capillary bed of tiny vessels in which single cancer cells or clumps of cells can lodge. By contrast, many common skin cancers (with the singular exception of malignant melanoma) are invasive but not metastatic, so they can be cured by simple excision of the tumour together with a decent margin of surrounding tissue. This emphasizes the seriousness of metastasis in the pathology of cancer. It is also salutary that in many instances cancer patients present with clear evidence of metastatic disease, such as secondary tumours radiologically visible in the lung, but no sign of the primary lump. It may take all the skill of an experienced histopathologist to indicate the probable origin of the diseased cells, knowledge of which is likely to be crucial for any form of clinical management.

Cancer therapy involves four modalities which may be employed singly or in combination: surgery, radiotheraphy, chemotherapy, or a group of less well-defined treatments, of which immunotherapy is the chief example. It is common practice to employ surgery where applicable (to reduce the tumour burden if a single large mass has been detected e.g. by X-rays or magnetic resonance imaging), followed by localized or whole-body radiotherapy to attack residual disease, and/or chemotherapy to deal with distant metastases. If the disease is advanced, with obvious metastasis, chemotherapy with a cocktail of three or four powerfully cytotoxic drugs may be the only worthwhile option. Most of these drugs are DNA-reactive chemicals which directly attack the genetic blueprints of the rogue cells. Alternatively a massive dose of whole-body irradiation may be attempted, and the patient rescued from death due to destruction of his bone marrow by subsequent reimplantation of his own marrow cells, collected prior to treatment and ‘cleaned up’ in vitro (autologous bone marrow transplantation).

Cancer is increasingly seen as a lifestyle disease, caused at least partly by environmental influences, with important modulation by the genetic inheritance of the individual. Sometimes viral infections may start the process off. In other cases sunlight is to blame, particularly in causing skin cancers among fair-skinned Caucasians living in tropical countries or under the ozone hole of the Southern hemisphere. Sometimes it is diet which seems to trigger disease, especially of the gastrointestinal tract: here fats are held suspect, and a high-fibre diet rich in cereals and vegetables is to be recommended. But far and away the most serious, and preventable, environmental cause of cancer is tobacco smoking, which is inexorably linked to cancer of the lung. On this conclusion the epidemiological evidence is stark — witness the sharp continuing rise in lung cancer among women in the Western world, which correlates precisely with the changes in social attitudes to smoking over the last 50 years.

One of the hottest areas of cancer research by the end of the twentieth century was the identification of genes that impart an inherited susceptibility to cancer of particular organs, or to cancer in general. Early successes have been the discovery of BRCA1 and BRCA2, genes which predispose to breast cancer — still the most common form of malignancy in Western women — and there are more to come. Other cancer-prone individuals carry genes whose products are enzymes known to be intimately associated with the biological phenomena of cell signalling, gene transcription, or DNA repair. A picture is beginning to emerge of cancer development, starting with a single cell exposed to some external influence, which causes a mutation in one of a small number of critical genes, ‘initiating’ the process of escape from growth control. Other genetic changes, leading to aneuploidy (abnormalities in the nature or the number of chromosomes), follow over a period which may be as long as several years, while so-called ‘promoter’ substances exacerbate the multiplication of the abnormal cells into a small tumour, which begins to invade its surroundings and may start to metastasise. In the later stages of disease the cells enter a ‘progression’ phase, in which gross rearrangements of their genetic make-up occur — these, can be seen down the microscope as wholesale redistribution of chromosomes, involving deletions, translocations, breaks, duplications, and doubtless many more subtle changes. Genetic instability can proceed to a state of chromosomal chaos — a ‘point of no return’ whereby cells cannot revert to the normal karyotype (the characteristics of its chromosomes) and must be killed. At that stage the disease is rampant and only the most aggressive intervention, including treatment with drugs which have dire toxic side-effects, is likely to produce any relief or remission, and cure is most unlikely. Often the side-effects (hair loss, vomiting and diarrhoea, neurological disorders, or bone marrow suppression) are so serious as to be unacceptable to the sick patient, and palliative treatment with powerful opiates is all that can be recommended. The most recent scientific findings emphasize the importance in tumour control of programmed cell death (apoptosis) and shortening of the far end, of the ‘arms’ of chromosomes (the telomeres) during replication. Chemotherapeutic and radiotherapeutic strategies induce apoptosis, so escape from programmed death signals is important.

— M. J. Waring

See also chemotherapy; radiotherapy.

n

Definition: malignancy
Antonyms: benignancy, benignity

Any one of a group of diseases characterized by unregulated cell division that gives rise to malignant tumours. Such tumours invade and destroy the tissues in which they originate and can spread to other parts of the body via the blood or lymphatic system or across a body cavity, such as the abdomen or chest. These secondary tumours, or metastases, are usually the cause of death, not the primary tumour. Tumours may be classified as solid tumours (usually occurring in an organ, such as the lung, stomach, or ovary), soft-tissue tumours (occurring in such tissue as muscle), leukaemias (cancers of the blood-producing tissue in the bone marrow characterized by overproduction of abnormal or immature forms of white blood cells), and lymphomas (cancers of the lymphatic system). Leukaemias are further classified according to the rate of progression of the disease (acute or chronic) and the type of white cell involved (e.g. hairy cell leukaemia, lymphoblastic leukaemia). Lymphomas are divided into Hodgkin's disease and non-Hodgkin's lymphomas, according to their appearance under the microscope.

Cancer can occur at any age, but the incidence of most cancers rises sharply after the age of 60 years. In the Western world the most common cancers are those of the lung, breast, skin, gut, and prostate gland. Cancer is treated by a combination of surgery, radiotherapy, and/or chemotherapy (see cytotoxic drugs), depending on the site and type of tumour.

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Definition

Cancer is a group of diseases characterized by uncontrolled growth of tissue cells in the body and the invasion by these cells into nearby tissue and migration to distant sites.

Description

Cancer results from alterations (mutations) in genes that make up DNA, the master molecule of the cell. Genes make proteins, which are the ultimate workhorses of the cells, responsible for the many processes that permit humans to breathe, think, and move, among other functions. Some of these proteins control the orderly growth, division, and reproduction of normal tissue cells. Gene mutations can produce faulty proteins, which in turn produce abnormal cells that no longer divide and reproduce in an orderly manner. These abnormal cells divide uncontrollably and eventually form a new growth known as a tumor or neoplasm. A healthy immune system can usually recognize neoplastic cells and destroy them before they divide. However, mutant cells may escape immune detection and become tumors or cancers.

Studies of the origins of cancer have shown that a combination of genetic influences and environmental causes over time triggers gene mutations, which may explain why most cancers are seen in adults of middle age or older (60%) and cancer is rare children. Many cancers have been shown to result from exposure to environmental toxins (carcinogens) and related alterations in DNA. Faulty DNA can also be inherited, predisposing an individual to develop cancer, although fewer than 10 percent of cancers are purely hereditary. Hereditary links have been shown in cancers of the breast, colon, ovaries, and uterus. Inherited physiological traits can also contribute to cancer, such as inheriting fair skin increasing the risk of skin cancer, but only if accompanied by prolonged exposure to intensive sunlight.

Tumors can be benign or malignant. A benign tumor is not cancer. It is slow growing, does not invade surrounding tissue, and once removed, does not usually recur. A malignant tumor is cancerous. It invades surrounding tissue and spreads to nearby or distant organs (metastasis). If the cancer cells have spread to surrounding tissue, even after the malignant tumor is removed, it will typically recur.

Cancer falls into several general categories:

• Carcinoma (90% of all cancer) are solid tumors arising in the layer of cells (epithelium) covering the body's surface and lining internal organs and glands. Adenocarcinomas develop in an organ or gland and squamous cell carcinomas originate in the skin.
• Melanoma originates in the skin, usually in pigment cells (melanocytes).
• Sarcoma is cancer of supporting tissue such as bone, muscle, and blood vessels.
• Leukemias and lymphomas are cancers of the blood and lymph glands.
• Gliomas are cancers of the nerve tissue.

The most common cancers affecting adults are cancer of the skin, lung, colon, breast, and prostate. Cancer of the kidneys, ovaries, uterus, pancreas, bladder, rectum, and the leukemias and lymphomas are among the 12 major cancers affecting Americans of all ages. Although children and adolescents do develop solid tumors, the most common high-risk cancers among children are:

• acute myeloid leukemia
• acute lymphoblastic leukemia
• neuroblastoma
• glioma
• sarcoma of bone (osteosarcoma) and soft tissue

Demographics

Childhood cancer is rare, occurring in about 14 in 100,000 children in the United States each year. However, in the entire U.S. population, one of every four deaths is from cancer, second only to deaths from heart disease. About 1.2 million cancer cases are diagnosed annually and more than 500,000 die, of whom 2,700 are children or adolescents.

Causes and Symptoms

Genetic predisposition, environmental causes, and individual developmental problems are responsible for most childhood cancer. The presence of other disorders, such as Down syndrome, has also been shown to be associated with cancer in children. The major risk factors that apply to adult cancer are tobacco, alcohol, sexual and reproductive behavior, and occupation, none of which increases risk in children. Other well-known risk factors, such as family history, infectious agents, diet, environmental toxins, and pollution, can apply equally to children.

Tobacco

Approximately 80 to 90 percent of lung cancer cases occur in smokers. Smoking is also the leading cause of bladder cancer and has been shown to contribute to cancers of the upper respiratory tract, esophagus, larynx, kidney, pancreas, stomach, and possibly breast as well. Second-hand smoke (passive smoking) has been shown to increase cancer risk in children and adults who live with smokers.

Infectious Agents

Cancer deaths worldwide can be traced to viruses, bacteria, or parasites. Epstein-Barr virus (EBV), for example, is associated with lymphoma, the hepatitis viruses are associated with liver cancer, HIV is associated with Kaposi's sarcoma, and the bacteria Helicobacter pylori is associated with stomach cancer.

Genetic Predisposition

Certain cancers such as breast, colon, ovarian, and uterine cancer recur generation after generation in some families. Eye cancer (retinoblastoma), a type of colon cancer, and early-onset breast cancer have been shown to be linked to the inheritance of specific genes.

Environmental Sources

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

Pollution

Studies have established links between environmental toxins, such as asbestos, and cancer. Chlorination of water may account for a small rise in cancer risk. However, the main danger from pollutants occurs when toxic industrial chemicals are released into the surrounding environment. As of 2004 an estimated 1 percent of cancer deaths are believed to be due to air, land, and water pollution.

Cancer is a progressive disease that goes through several stages, each producing a number of symptoms. Early symptoms can be produced by the growth of a solid tumor in an organ or gland. A growing tumor may press on nearby nerves, organs, and blood vessels, causing pain and pressure that may be the first warning signs of cancer. Other symptoms can include sores that do not heal, growths on the skin or below the skin, unusual bleeding, difficulty digesting food or swallowing, and changes in bowel or bladder function. Fever can be present as well as fatigue and weakness.

When to Call the Doctor

Despite the fact that there are hundreds of different types of cancer, each producing different symptoms, the American Cancer Society has established the following seven symptoms as possible warning signals of cancer:

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

Parents should report any such symptoms to the pediatrician along with unexplained fever or frequent infections. Vision problems, weight loss, lack of appetite, depression, swollen glands, paleness, or general weakness are other reasons for parents to consult the pediatrician. Generally, the earlier cancer is diagnosed and treated, the better the chance of a cure, although not all cancers have early symptoms.

Diagnosis

Diagnosis begins with a complete medical history, including family history of cancer, and a thorough physical examination. The doctor observes and palpates (applies pressure by touch) different parts of the body in order to identify any variations from normal size, feel, and texture of an organ or tissue. The doctor looks inside the mouth for abnormalities in color, moisture, surface texture, or the presence of any thickening or sores in the lips, tongue, gums, the roof of the mouth, or the throat. The doctor observes the front of the neck for swelling and may gently manipulate the neck and palpate the front and side surfaces of the thyroid gland at the base of the neck, looking for nodules or tenderness. The doctor also palpates the lymph nodes in the neck, under the arms, and in the groin, looking for enlargement. The skin is examined for sores that are slow to heal, especially those that bleed, ooze, or crust; irritated patches that may itch or hurt; and any change in the size of a wart or a mole.

In adolescent females, a pelvic exam may be conducted to detect cancers of the ovaries, uterus, cervix, and vagina. The doctor first looks for abnormal discharges or the presence of sores. Then the internal pelvic organs such as the uterus and ovaries are palpated (touched while applying gentle pressure) to detect abnormal masses. Breast examination evaluates unevenness, discoloration, or scaling; both breasts are palpated to feel for masses or lumps.

In adolescent males, inspection of the rectum and prostate may be included in the physical examination. The doctor inserts a gloved finger into the rectum and rotates it slowly to feel for growths, tumors, or other abnormalities. The testes are examined visually, looking for unevenness, swelling, or other abnormalities. The testicles are palpated to identify lumps, thickening or differences in size, weight, or firmness.

If an abnormality is detected on physical examination, or symptoms suggestive of cancer are noted, diagnostic tests will be performed. Laboratory studies of sputum, blood, urine, and stool can detect abnormalities that may confirm cancer. Sputum cytology involves the microscopic examination of phlegm that is coughed up from the lungs. Tumor markers, specific proteins released by certain types of cancer cells, can be detected by performing a test on venous blood. If leukemia or lymphoma is suspected, a complete blood count (CBC) with peripheral smear (differential) is done to evaluate the number, appearance, and maturity of red blood cells (RBCs) and white blood cells (WBCs) and to measure hemoglobin, hematocrit, and platelet count. A bone marrow biopsy may be done to determine what type of cells is present in the bone marrow. Blood chemistries will be done to help determine if liver or kidney problems are present. Blood chemistries are also useful in monitoring the effectiveness of treatment for all types of cancer and in following the course of the disease and detecting recurrences.

Diagnostic imaging techniques such as computed tomography (CT scans), magnetic resonance imaging (MRI), ultrasound, and fiberoptic scope examinations (such as colonoscopy or sigmoidoscopy) can help determine the location, size, and characteristics of a tumor even if it is deep within the body. Conventional x rays are often used for initial evaluation, because they are relatively cheap, painless, and easily accessible. In order to increase the information obtained from a conventional x ray, air or contrast media (such as barium or iodine) may be used to enhance the images.

The most definitive diagnostic test for cancer is a biopsy, which is the surgical removal of a piece of suspect tissue for staining and microscope examination (cytochemistry). By examining certain cell characteristics, abnormalities can be identified and the presence of specific types of cells can be diagnostic for certain cancers. The biopsy provides information about the type of cancer, its stage, the aggressiveness of the cancer in invading nearby tissue or organs, and the extent of metastases at diagnosis. The pathologist who evaluates cancer cells in biopsied tissue designates the cancer as being stage I, II, III, or IV, in terms of the degree of metastasis.

Newer molecular and cellular diagnostic testing, such as polymerase chain reaction (PCR), allows the molecular genetic analysis of tumors. Cytogenetic analysis of tumor chromosomes, for example, can identify structural abnormalities that may explain the unique origins of cancer in an individual child. Spectral karyotyping (SKY), an advanced method of screening chromosomes for numeric and structural abnormalities, is used to evaluate pediatric tumors. Gene sequences can also be evaluated in a method (comparative genomic hybridization) that compares samples from a tumor and normal tissue after both have been exposed to the same radioactive material. This method can determine gains and losses in DNA in the region of the tumor, detecting alterations that have caused the cancer. The developing science of proteomics studies specific proteins in cells and may someday be able to provide detailed assessment of cancer cells.

Treatment

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

Cancer treatment is always tailored to the individual. The treatment choice depends on the type and location of cancer, the extent to which it has already spread, and the age, sex, and general health status of the individual. The major types of treatment are: surgery, radiation, chemotherapy, immunotherapy, hormone therapy, and bone-marrow transplantation.

Advances in molecular biology and cancer genetics have contributed greatly to the development of therapies that provide cell-targeted treatment. Genetic testing uses molecular probes to identify gene mutations that have been linked to specific cancers. In the early 2000s ongoing research is focused on new treatment and prevention methods, including molecular-targeted therapies, virus therapy, immunotherapy, and drug therapy that stimulates the self-destruction of cancer cells (apoptosis).

Targeted molecular therapy, although as of 2004 still the subject of concentrated research, was being used effectively in pediatric study subjects where it has been shown to reduce the toxicity seen with conventional chemotherapy. Unlike chemotherapy, which treats all cells uniformly, targeted molecular therapy can focus on selected cells without affecting normal cells and tissues. This refinement frees children from some of the long-term toxic effects and complications that can negatively affect quality of life and survival even if the cancer is cured.

Surgery

Surgical removal of a solid tumor is most effective with small tumors confined to one area of the body. Surgery removes the tumor (tumor resection) and usually part of the surrounding tissue to ensure that no cancer cells remain in the area. Since cancer usually spreads via the lymphatic system, adjoining lymph nodes are sometimes removed as well. Surgery may also be preventive or prophylactic, removing an abnormal looking area of tissue that is likely to become malignant over time. During surgery biopsies may also be performed on tissue that may be affected by metastases. Surgery is not a typical treatment for leukemia or lymphoma, which arise in the circulatory system and lymphatic systems that extend throughout the body. Children with osteosarcoma (bone cancer) and other solid tumors are candidates for surgery, however.

Surgery may be performed in conjunction with radiation (cytoreductive surgery) or chemotherapy. The surgeon removes as much of the cancer as possible and the remaining area is treated with radiotherapy or chemotherapy or both. In advanced metastatic cancer when cure is unlikely, palliative surgery aims at reducing symptoms. Debulking surgery, for example, removes part of a tumor that is pressing on other organs and causing pain. In tumors that are dependent on hormones, one option is to remove organs that secrete the hormones.

Radiation Therapy

Radiation kills tumor cells and is used alone when a tumor is in a poor location for surgery. More often, it is used in conjunction with surgery and chemotherapy. Radiation can be either external or internal. External radiation is aimed at the tumor from outside the body. In internal radiation (brachytherapy), radioactive liquid or pellets are delivered to the cancerous site via a pill, injection, or insertion in a sealed container.

Chemotherapy

Chemotherapy is the administration of drugs that kill cancer cells (cytotoxic drugs). It destroys hard-to-detect cancer cells that have spread (metastasized) through the circulation or lymph system. Chemotherapeutic drugs are given orally or intravenously, either alone or in conjunction with surgery, radiation, or both. When chemotherapy is used before surgery or radiation, it is known as primary chemotherapy or neoadjuvant chemotherapy. Because the cancer cells have not yet been exposed to anti-cancer drugs, they are especially vulnerable, allowing neoadjuvant therapy to effectively reduce tumor size. However, the toxic effects of neoadjuvant chemotherapy may be severe, because normal cells are also destroyed. Chemotherapy may also make the body less tolerant of the side effects of other treatments such as radiation therapy. Adjuvant therapy is the more common type of chemotherapy, used to enhance the effectiveness of other treatments.

Immunotherapy

Immunotherapy uses the body's own immune system, specifically a type of disease-fighting white cell called T-cells, to destroy cancer cells. Tumor-specific proteins that are part of unique genetic mutations in pediatric cancer, for example, are believed to be ideal targets for anti-tumor immune processes. Various immunological agents are as of 2004 still in clinical trials and are not as of that year widely available, though initial results are promising. Monoclonal antibodies are used to

Common childhood cancers
Percentage of total childhood cancers	Type of cancer
SOURCE: Margo Hoover-Regan. http://www.csupomona.edu/~cancerbio/pediatric%20cancer%20-%20Dr.%20Hoover-Regan.htm. Updated May 15, 2000.
39%	Leukemia (white blood cell cancer) and lymphoma (lymph system cancer)
20.7%	Brain cancers (brain and spinal cord tumors)
7.3%	Neuroblastoma (nerve cell cancer, most commonly in the adrenal gland)
6.1%	Wilms' tumor (kidney cancer that can metastasize to lung)
4.7%	Osteosarcoma (bone cancer) and Ewing's sarcoma (cancer in the bone shaft)
3.4%	Rhabdomyosarcoma (muscle tissue cancer, most often in head and neck)
2.9%	Retinoblastoma (malignant eye tumor)
16.4%	Germ cell cancer (ovarian or testicular cancers) and others

fight cancer cells in much the same way as antibodies that are produced by the body's own immune system work to fight infection. Other substances are also being used experimentally. They include substances such as interferons, interleukins, growth factors, monoclonal antibodies, and vaccines. Unlike traditional vaccines, cancer vaccines do not prevent cancer but are designed to treat existing disease. They work by boosting the immune system and training immunized cells to destroy cancer cells.

Hormone Therapy

Hormone therapy is standard treatment for cancers that are hormone-dependent and grow faster in the presence of specific hormones, such as cancer of the prostate, breast, and uterus. Hormone therapy blocks the production or action of these hormones, slowing growth of the tumor and extending survival for months or years.

Bone Marrow Transplantation

Bone marrow is the tissue within bone cavities that produces blood cells. Healthy bone marrow tissue constantly replenishes the blood supply and is essential to life. Sometimes drugs or radiation needed to destroy cancer cells also destroys bone marrow and only replacement with healthy cells counteracts this adverse effect. A bone marrow transplant involves removing marrow from a donor and transplanting blood-forming cells to a recipient. While not a therapy in itself, bone marrow transplantation may allow a cancer patient to undergo aggressive therapy.

Many specialists work together to treat cancer patients. The oncologist is a physician who specializes in cancer care and usually coordinates the treatment plan, directing chemotherapy, hormone therapy, and any treatment that does not involve radiation or surgery. The radiation oncologist uses radiation to treat cancer, while the surgical oncologist performs surgery to diagnose or treat cancer. Gynecologist-oncologists and pediatric-oncologists, as their titles suggest, are physicians who treat women's and children's cancers. Radiologists read the x rays, ultrasound images, CT scans, and MRI images to help diagnose cancer. Hematologists specialize in disorders of the blood and bone marrow and are consulted in the evaluation of leukemia, lymphoma, and bone cancer.

Alternative Treatment

A range of alternative treatments are available to help treat cancer that can be used in conjunction with, or separate from, surgery, chemotherapy, and radiation. Alternative treatment of cancer is a complicated arena and a trained complementary health practitioner should be consulted.

Although the effectiveness of complementary therapies such as acupuncture in alleviating cancer pain have not as of 2004 been clinically proven, many cancer patients find it safe and beneficial. Bodywork therapies such as massage and reflexology ease muscle tension and may alleviate side effects such as nausea and vomiting. Homeopathy and herbal remedies used in Chinese traditional herbal medicine also have been shown to alleviate some of the side effects of radiation and chemotherapy and are being recommended by many doctors.

Prognosis

Most cancers show good cure rates if detected and treated at early stages. The prognosis involves the type of cancer, its degree of invasiveness, and the extent of metastases at diagnosis. In addition, age, general health status, and response to treatment are important factors. Cancer deaths in children have shown consistent declines, decreasing between 1975 and 2000 from 50 in 1 million diagnosed to 25 in 1 million. However, cancer is the leading cause of death among children and adolescents, responsible for 2,700 deaths each year in the United States.

Prevention

Prevention of cancer means being aware of causes and risks, which involve a combination of genetic and environmental factors. Except for family history, specific genetic causes or an inherited predisposition are generally unknown in individuals until revealed in the diagnostic process. Known environmental causes can be avoided, however. A list of guidelines offered by nutritionists and epidemiologists from leading U.S. universities to reduce the risk of cancer includes some that may apply to children and adolescents:

• Eat plenty of vegetables and fruits, especially cruciferous vegetables such as broccoli, cauliflower, and cabbage.
• Decrease or avoid eating animal fats and red meats.
• Exercise vigorously for at least 20 minutes every day.
• Avoid excessive weight gain.
• Avoid tobacco (including second hand smoke).
• Avoid excessive amounts of alcohol.
• Avoid midday sun (between 11 a.m. and 3 p.m.) when rays are the strongest.
• Avoid risky sexual practices and multiple partners.
• Avoid known carcinogens in the environment or work place.

Certain drugs being used as of 2004 for treatment could also be suitable for prevention, at least prevention of recurrences. For example, the drug tamoxifen has been very effective against breast cancer and is in 2004 being used to prevent recurrence in breast cancer survivors. Similarly, retinoids derived from vitamin A are being tested for their ability to slow the progression of or to prevent head and neck cancers. Certain studies suggest that cancer incidence is lower in areas where soil and foods are rich in the mineral selenium.

Nutritional Concerns

Certain foods, including many vegetables, fruits, and grains, are believed to offer protection against various cancers. In laboratory studies, vitamins such as A, C, and E, as well as beta-carotene found in carrots and isothiocyanate and dithiolthione compounds found in cruciferous vegetables, such as broccoli, cauliflower, and cabbage, have been shown to provide protection against certain types of cancer. Studies have shown that eating a diet rich in fiber as found in fruits, vegetables, and whole grains can reduce the risk of colon cancer.

Parental Concerns

A diagnosis of childhood cancer raises many uncertainties and concerns for parents, including how to acquire the most effective therapy. Advances in molecular and cellular technologies have improved both the diagnosis and treatment of pediatric cancer and also carry with them the possibility of someday curing and preventing cancer in children. While cancer was at one time nearly always fatal in children, as of 2004 more than 75 percent of children diagnosed with cancer enjoyed disease-free survival. Targeted molecular therapy and immunotherapies are the ongoing focus of concentrated research, and studies using these cell-selective technologies in treating children have shown encouraging results, both in earlier responses and reduced toxicity and complications longer term. Parents can be assured of access to the current knowledge base in molecular biology and advanced treatment technologies that promise better outcomes.

See also Leukemias, acute; Leukemias, chronic.

Resources

Books

Janes-Hodder, Honna, et al. Childhood Cancer: A Parent's Guide to Solid Tumor Cancers, 2nd ed. Cambridge, MA: O'Reilly Media Inc., 2002.

Woznick, Leigh A., and Carol D. Goodheart. Living with Childhood Cancer: A Practical Guide to Help Families Cope. Washington, DC: American Psychological Association (APA), 2002.

Organizations

American Cancer Society. 1599 Clifton Road, NE, Atlanta, GA 30329. Web site: www.cancer.org.

Cancer Research Institute (National Headquarters). 681 Fifth Avenue, New York, NY 10022. Web site: www.cancerresearch.org.

National Cancer Institute. 9000 Rockville Pike, Building 31, room 10A16, Bethesda, MD 20892. Web site: wwwicic.nci.nih.gov.

National Children's Cancer Society. 1015 Locust Suite 600, St. Louis, MO 63101. Web site: www.nationalchildrenscancersociety.com.

Web Sites

"Childhood Cancer." Kid's Health, 2004. Available online at www.kidshealth.org/parent/medical/cancer/cancer.html (accessed December 8, 2004).

[Article by: L. Lee Culvert Rosalyn Carson-DeWitt, MD Teresa G. Odle]

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Cancer is the end product of a multistep process (carcinogenesis) that occurs over many years. The term "cancer" actually refers to numerous distinct diseases characterized by abnormal cell growth and differentiation. Cancers are categorized by the organ and/or cell of origin. For example, squamous cell carcinoma of the lung arises from pulmonary epithelial tissue, whereas adenocarcinoma of the breast arises from mammary duct epithelium. The natural history of a cancer is highly dependent on the organ and cell type from which it is derived. In addition, prognosis is influenced by the stage and histologic grade of the cancer. Staging is generally designated by the TNM (tumor, nodes, metastasis) staging system, which takes into account the size of the primary tumor(T), the extent to which local lymph nodes (glands) are involved (N), and whether or not distant metastases are present (M). The histologic grade, determined by microscopic examination of the biopsy specimen, provides an objective assessment of the degree of cellular differentiation.

Incidence, Prevalence, and Mortality

The worldwide burden of cancer is a major health problem, with more than 8 million new cases and 5 million deaths per year. The burden from cancer may be described in terms of incidence (number of new cases per 100,000 each year), prevalence (number of people at a given point in time with a cancer diagnosis), and mortality (number of cancer deaths). With few exceptions, cancer incidence, prevalence, and mortality rates are higher in industrialized countries (e.g., United States, European nations) than in developing countries (e.g., African nations, China). Incidence rates for specific cancers can be dramatically affected by the use of screening procedures to identify asymptomatic disease. This is illustrated by the dramatic increase in the incidence of prostate cancer that accompanied the introduction of prostate-specific antigen (PSA) screening in the late 1980s. Similarly, prevalence rates may be a poor index for comparing cancers, because they are dependent upon incidence, natural history, and treatment efficacy. For example, due to the relatively short life expectancy of individuals with pulmonary neoplasms, the prevalence of lung cancer is much lower than that of prostate cancer, despite the higher mortality rates associated with lung cancer. In addition to the impact of screening and natural history, prevalence rates increase as treatment improves, because therapeutic advances enable individuals to live longer following a cancer diagnosis.

Worldwide, lung cancer is the leading cause of cancer mortality, followed by stomach cancer. Smoking remains the leading preventable cause of cancer, and mortality and incidence rates of lung cancer rise and fall with smoking rates. The current trend shows a leveling off of smoking-related cancers in developed countries, possibly because of health-promotion and disease-prevention efforts. Geographical variations occur in cancer incidence and mortality, with Africa and Asia generally having lower rates than North America and Europe. However, it has been noted that differences in data collection and diagnostic practices make worldwide cancer comparisons somewhat difficult. Overall, worldwide incidence rates of breast, colon and rectum, and prostate cancers are highest in developed countries, while cancers of the cervix, mouth and pharynx, esophagus, and liver are higher in developing countries. Migration studies generally report that migrants from developing countries to developed countries adopt cancer incidence rates equivalent to those of their new country. For example, studies of Japanese and Chinese immigrants living in the United States show that their risks for prostate and breast cancers increase dramatically the longer they reside in the United States. Similar trends for increased risk are seen among African immigrants in European countries. Geographical variations in cancer incidence and mortality also exist in the United States. Each cancer site shows some variation, such as higher prostate cancer mortality rates in the South Central and southern Atlantic states, and higher breast cancer mortality rates in the northeastern states. The Atlas of United States Mortality, published by the Centers for Disease Control and Prevention, provides detailed geographic information on cancer mortality rates in the United States, and is available online at http://www.cdc.gov/nchs/data/atlasmet.pdf.

In the United States, cancer is the second leading cause of death; although there has been a slight decline in the number of people dying from cancer since 1990, with more than one-half of those who develop cancer being cured or surviving for over five years. Because cancer is many diseases, some cancers are more common and/or more curable than others. For example, although nonmelanoma skin cancer, mainly caused by overexposure to ultraviolet (UV) radiation from the sun, is responsible for the largest number of new cancer cases each year, mortality rates associated with it are low.

Incidence, prevalence, and mortality in the United States vary by cancer site, between whites and blacks, and between men and women. By order of incidence, the three most common cancers in men are prostate, lung, and colorectal; in women the three most common cancers are breast, lung, and colorectal. These cancer sites represent more than one-half of both new cases of cancer and deaths from cancer each year. Lung cancer is the leading cause of death from cancer for men and women, accounting for almost one-third of cancer deaths.

Although cancer risk increases with age, malignant diseases are an important cause of morbidity and mortality in the pediatric population. The most frequent cancers in children are leukemias, tumors of the nervous systems, lymphomas, soft-tissue sarcomas, and kidney tumors. Other than lung cancer, which increases dramatically after age forty, three out of every four deaths from cancer occur in individuals older than sixty years of age.

Causes of Cancer

Environmental and lifestyle factors such as tobacco use, diet, alcohol consumption, and exposure to sunlight play a primary role in the development of the majority of cancers. In addition, exposure to occupational factors and to specific pathogens (e.g., viruses, bacteria), hormones, and radiation also contributes to cancer at particular sites. However, the question still remains as to why one person exposed to a given environmental or lifestyle risk factor develops cancer and another person does not. The importance of hereditary factors (gene-environment interactions) cannot be overemphasized in this regard. True "hereditary cancers," those attributable to specific genes that are passed from one generation to another, account for only a small proportion of cancer cases, however.

Exposure to carcinogens in tobacco smoke accounts for almost one-third of cancer cases, especially cancers of the lung, respiratory tract, esophagus, bladder, pancreas, and, most likely, cancers of the stomach, liver, and kidneys. Carcinogens found in the environment and the workplace (e.g., asbestos, benzene, vinyl chloride compounds, dyes, arsenic, petroleum products) and cancers associated with exposure to these chemicals (e.g., lung and bladder) are higher in urban areas than in rural areas. Diet also influences the risk of cancer, although researchers are unsure of the mechanisms involved. In general, evidence supports an increased risk of various cancers (e.g., colon, rectum) with a high intake of red meats, and a decreased risk of various cancers (e.g., lung, colon, stomach) with a high intake of vegetables and fruits. Other food constituents, such as vitamins and minerals, are also being investigated for their ability to prevent cancer.

Other possible causes of cancer include pathogens, such as hepatitis B and C viruses in liver cancer, and the Helicobacter pylori bacterium in stomach cancer. Hormonal factors contributing to cancer have focused on estrogen, progesterone, and testosterone, and their role in reproductive organ cancers. These steroid hormones are being investigated because they influence the growth of cells, particularly those of the prostate, ovary and cervix, and breast. Radiation exposure, especially UV radiation from the sun, is a significant contributor to cancer of the skin, and using sunscreens has been shown to reduce skin cancer risk.

Interactions between genes and environmental exposures are of great importance in determining one's risk of developing cancer. For instance, genes and nutrients can interact to increase or decrease the risk of cancer depending on genetic variations known as polymorphisms—different forms of the same gene that may either increase or decrease the risk of cancer. For example, different polymorphisms in the gene that determines how vitamin D is metabolized can influence the risk of prostate cancer; one polymorphism is associated with increased risk of prostate cancer and another is associated with decreased risk. Polymorphisms in the genes that are responsible for repairing radiation damage to skin cells also play a role in increasing or decreasing cancer risk.

Cancer Prevention and Treatment

Many cancer risk factors are avoidable. Preventing cancer by attention to diet and by quitting or never starting smoking are the most significant strategies to reduce cancer risk. Prevention of cancer is being investigated in clinical trials on dietary patterns (high intake of vegetables and fruits; low intake of saturated fats) and dietary constituents such as vitamins, minerals, and soy. Future progress may depend partly on strategies such as chemoprevention—the use of natural or synthetic substances to prevent cancer cells from forming, progressing, or recurring. For example, the antiestrogen hormone tamoxifen has been shown to reduce the risk of developing breast cancer by 50 percent among women at high risk for this disease. It also has been shown to reduce the risk of developing a new primary breast cancer in the opposite breast among women with a history of breast cancer. Chemopreventive agents also are being investigated for prevention of colon, rectum, prostate, and lung cancers.

Screening and Early Detection

Mammography has been shown to reduce breast cancer mortality among women over the age of fifty, and Pap smear screening has dramatically reduced mortality from cervical cancer. In addition, there is growing evidence that fecal occult blood testing and endoscopic screening significantly reduce mortality from colorectal cancer. Identification of mutations is becoming an important tool for identifying individuals at high risk of various cancers. For instance, DNA repair-gene mutations (e.g., MSH2, PMS1) have been associated with a higher risk of colon cancer, as have mutations in the tumor suppressor genes BRCA1 and BRCA2 in breast cancer. Although it is believed that inherited risk for cancer accounts for a small proportion of total cancer cases each year, identifying this risk may help researchers determine how cancer develops and progresses, and may provide a tool for targeting prevention or treatment strategies.

Prognosis is dependent on the type of cancer diagnosed, the stage of the disease at the time of diagnosis, and the effectiveness of currently available therapy. Surgery, radiation, chemotherapy, hormonal therapy, and immunologic therapy form the basis of modern cancer treatment. Surgery is generally the treatment of choice for localized tumors, although radiation often is an appropriate alternative. Lasers are being used for small noninvasive tumors of the skin, cervix, and throat. Radiation therapy is often recommended as primary therapy (e.g., for Hodgkin's disease and early stage tumors of the head and neck), and is an important adjunct to lumpectomy for the treatment of breast cancer. Radiation therapy also plays an important role in the symptomatic management of patients with advanced cancer (e.g., bone or brain metastases). In contrast to surgery and radiation, chemotherapy is a systemic, rather than local, therapy, because the drugs are distributed throughout the body. Chemotherapy generally is required to treat advanced cancers that are not amenable to surgical removal or radiation therapy. Chemotherapy is often used after surgery (adjuvant therapy) to reduce the risk of relapse. The most common indication for adjuvant chemotherapy is following surgery for localized breast or colorectal cancer.

Hormone therapy represents a very important category of cancer treatment for breast cancer (tamoxifen and raloxifene) and prostate (androgen blockers) cancer. In addition, immunotherapy (also called biologic therapy) is being used to boost the immune system to fight cancer cells. Monoclonal antibodies are one type of immunotherapy that can be used to fight specific cancer cells or to carry chemotherapeutic agents to a tumor. Interferon is another immunotherapy that has shown promise in slowing the growth of tumors. Each of these treatments has advantages and disadvantages, and should be discussed with a physician.

Cancer in Developing Countries

Cancer trends are of great concern to the public health community. As developing countries become more industrialized, incidence and mortality rates for cancers of the breast, colon, rectum, and prostate begin to rise. Also, smoking is increasing worldwide—along with lung cancer incidence and mortality rates. Liver cancer shows the same trends as lung cancer, but for a different reason. Infection with the hepatitis B or C viruses is a major risk factor for liver cancer. In some countries, where a vaccine for hepatitis B is widely used to vaccinate infants, liver cancer incidence in later life has declined; however, incidence rates in developing countries, where vaccination is not widely available, appear to be increasing. Another virus, the human papillomavirus (HPV), is an important risk factor for cervical cancer. Cervical cancer and HPV are more common in equatorial countries (e.g., in Latin America, sub-Saharan Africa, and Southeast Asia) and less common in countries in northern latitudes. Screening and treatment for early stages of cervical cancer have made significant inroads for reducing the incidence and mortality of this disease.

(SEE ALSO: Breast Cancer; Carcinogen; Cervical Cancer; Colorectal Cancer; Environmental Determinants of Health; Environmental Tobacco Smoke; Genetics and Health; Geography of Disease; Geriatrics; Incidence and Prevalence; Lung Cancer; Melanoma; Mortality Rates; Nutrition; Occupational Safety and Health; Oral Cancer; Ovarian Cancer; Prevention; Preventive Health Behavior; Prostate Cancer; Screening; Skin Cancer)

Bibliography

Doll, R., and Peto, R. (1981). "The Causes of Cancer: Quantitative Estimates of Avoidable Risks of Cancer in the United States Today." Journal of the National Cancer Institute 66:1191–1308.

Fleming, I. D.; Cooper, J. S.; Henson, D. E.; Hutter, >R. V. P.; Kennedy, B. J.; Murphy, G. P.; Sullivan, B. O.; Sobin, L. H.; and Yarbro, J. W. (1997). AJCC Cancer Staging Manual, 5th edition. New York: Lippincott Williams & Wilkins.

Greenlee, R. T. (2000). "Cancer Statistics, 2000." CA: A Cancer Journal for Clinicians 50:7–33.

Greenwald, P.; Kramer, B. S.; and Weed, D., eds. (1995). Cancer Prevention and Control. New York: Marcel Dekker.

Lichtenstein, P.; Holm, N. V.; Verkasalo, P. K.; Iliadou, A.; Kaprio, J.; Koskenvuo, M.; Pukkala, E.; Skytthe, A.; and Hemminki, K. (2000). "Environmental and Heritable Factors in the Causation of Cancer— Analyses of Cohorts of Twins from Sweden, Denmark, and Finland." New England Journal of Medicine 343(2):78–85.

Parkin, D. M.; Pisani, P.; and Ferlay, J. (1999). "Global Cancer Statistics." CA Cancer J Clin 49(1):33–64.

—— (1999). "Estimates of the Worldwide Incidence of 25 Major Cancers in 1990." International Journal of Cancer 80(6):827–841.

Pickle, L. W.; Mugiole, M.; Jones, G. K.; and White, A. A. (1996). Atlas of United States Mortality. Hyattsville, MD: U.S. Department of Health and Human Services (DHHS Publication No. [PHS] 97–1015).

Pisani, P.; Parkin, D. M.; Bray, F.; and Ferlay, J. (1999). "Estimates of the Worldwide Mortality from 25 Cancers in 1990." International Journal of Cancer 83(1):18–29.

Schottenfeld, D., and Fraumeni, J. F., Jr., eds. (1996). >Cancer Epidemiology and Prevention, 2nd edition. New York: Oxford University Press.

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World Cancer Research Fund (1997). Food, Nutrition and the Prevention of Cancer: A Global Perspective. Washington, DC: American Institute for Cancer Research.

— HOWARD L. PARNES; DARRELL ANDERSON

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Cancer is a number of related diseases that are characterized by the uncontrolled proliferation and disorganized growth of cells. Tumor cells invade and destroy normal tissues and may spread throughout the body via the circulatory systems.

A Genetic Disease

Cancer is the result of changes in the genetic material of a cell that cause the cell to gradually lose the ability to grow in a regulated fashion. These changes can be brought about by contact with harmful environmental agents or by inheritance of genes leading to a genetic predisposition.

Cancer risk increases with age, as the probability of accumulating mutations in the DNA increases with time. Environmental factors include lifestyle (e.g., smoking), diet (e.g., saturated fats from red meat), and exposure to certain chemicals (e.g., asbestos, benzopyrenes), ionizing radiation (e.g., X-rays, radon gas), ultraviolet radiation (e.g., sun, tanning beds), and certain viruses (e.g., human papillomavirus, Epstein-Barr virus). Heredity also plays a role in oncogenesis, as mutations in certain genes increase the probability of developing certain types of cancer. For instance, women who inherit a mutated copy of the BRCA1 or BRCA2 gene have a greatly increased probability of developing breast cancer at a young age.

Classification of Cancer Types

The term "cancer" is general, in that it represents a large group of related diseases that arise from neoplasms. A neoplasm is classified by the type of tissue in which it arises and the stage to which it has progressed. Neoplasms are also called tumors. Not all tumors are cancerous. A tumor that grows in one place and does not invade surrounding tissue is called benign. In contrast, invasive tumors are called malignant. These are cancerous.

Table 1

ESTIMATED NEW CANCER CASES AND DEATHS IN THE UNITED STATES 2000
Site of Origin	New Cases*		Deaths*
	Male	Female	Male	Female
Breast	1,400	182,800	400	40,800
Colorectal	63,600	66,600	27,800	28,500
Esophagus	9,200	3,100	9,200	2,900
Kidney & Bladder	57,100	27,300	15,400	8,700
Leukemia	16,900	13,900	12,100	9,600
Liver	10,000	5,300	8,500	5,300
Lung	89,500	74,600	89,300	67,600
Lymphoid	35,900	26,400	14,400	13,100
Ovary	-	23,100	-	14,000
Pancreas	13,700	14,600	13,700	14,500
Prostate	180,400	-	31,900	-
Skin	34,100	22,800	6,000	3,600
Stomach	13,400	8,100	7,600	5,400
Testis	6,900	-	300	-
Uterine	-	48,900	-	11,100
*(the American Cancer Society's Clinical Oncology, Lenhard R.E., Osteen R.T., Gansler T., 2001)

Benign or Malignant Tumor

Whether a tumor is benign or malignant determines how potentially life-threatening it is. Benign tumors are usually harmless, although their location may be serious (if surgery to remove the tumor would carry significant risk). These tumors are not considered cancerous, are relatively slow-growing, and usually are encased within a fibrous capsule.

Malignant tumors (cancers) have great potential to spread, or metastasize, to other sites in the body. These tumors are fast-growing and aggressive, and they invade neighboring healthy tissue. They therefore are considered life threatening.

Type of Tissue

The body consists of many different organs, which in turn are composed of several different types of tissues. There are three major categories of tissue-related tumor types: carcinoma, sarcoma, and leukemia/lymphoma. There are also other specialized tumor categories, such as those of the central nervous system (e.g., brain tumors).

Carcinoma

This is the largest category, containing about 90 percent of all cancers, and it consists of neoplasms derived from epithelial cells. Epithelial cells make up the outer layers of the skin. They also line the inner structures of organs such as the lungs, intestines and testes, as well as complex tissue such as the breast.

Sarcoma

These are solid tumors derived from all connective tissues except the bloodforming tissues (these are the leukemias and lymphomas). These tumors account for about 2 percent of all cancers. They occur in such tissues as muscle, bone, and cartilage.

Leukemia and Lymphoma

This group contains about 8 percent of all cancers, including blood cancers that originate from the marrow (leukemias) and from the lymphatic system (lymphomas). This group also includes other nonsolid tumors of the bone marrow and lymphatic system, such as myeloma, which affects plasma cells—a type of white blood cell found in the marrow and in other tissues.

Type of Cell

Classifying a tumor by the type of cell from which it is derived is slightly more complex than classifying it by the type of tissue, since there are so many cell types. The main cell types include adenomatous cells (which are ductal or glandular cells), basal cells (found at the base of the skin), myeloid blood cells (granulocytes, monocytes, and platelets), lymphoid cells (lymphocytes or macrophages), and squamous cells (flat cells). Therefore it is possible for a cancer classified by its site of origin to be broken up into one of several cell types. For example, a skin cancer could be either a squamous cell carcinoma, a basal cell carcinoma, or a melanoma (from a pigment-producing cell).

Site of Origin

Solid tumors are firm masses that develop from a neoplasm's originating organ, such as the brain, esophagus, kidney, liver, lung, ovary, pancreas, prostate, or testis. Tumors of the blood-forming tissues and lymphatic systems are not solid and tend to remain free and circulating even when malignant. Some of the common forms of cancer are listed in the table above.

Cancer Progression

There two main steps in cancer progression: the initial growth of the cancer and the subsequent spread via metastasis. Solid tumors are subject to the physiological constraints of biological systems: Without nutrients and oxygen, they will die. Therefore a solid tumor is initially limited in size to no larger than 1 to 2 millimeters in diameter (about the size of a small pea).

For a tumor to become aggressive, it needs to be able to nourish the cells at the center of its mass that are too far away from blood vessels. This is achieved by angiogenesis. Through mutation, a few cancer cells may gain the ability to produce angiogenic growth factors. These growth factors are proteins that are released by the tumor into nearby tissues, where they stimulate new blood vessels to grow into the tumor. This allows the tumor to rapidly expand in mass and invade surrounding tissue. It also provides a route for the cancer cells to escape into the new blood vessels and circulate throughout the body, where they can lodge in other organs forming metastases.

The most common way for a cancer to metastasize is through the lymphatic system. The lymphatic system is a network of channels throughout the body that carry a tissue fluid called lymph.

When a primary neoplasm metastasizes to another location, its cell type does not change. If leukemia metastasizes to the liver and develops a tumor, the tumor will display the characteristics of the leukemia, not those of a liver cancer. In some cases this can help physicians determine the original site of a tumor.

Genes Altered in Tumors

Although each cell in the body maintains itself and carries out its specific function, it is part of a large colony of collaborating cells that constitute the whole organism. A cell communicates with its surrounding cells by releasing chemical messages, in a process called signal transduction. These messages bind to specific receptor proteins on the surface of the surrounding cells. The gene expression of these cells is changed as a result of the messages.

A hyperplastic cell or a cancerous cell will stimulate neighboring cells to grow by secreting growth factors. Several types of genes can be mutated in tumor cells: oncogenes, tumor suppressor genes, DNA repair genes, and genes involved in cell mortality.

Oncogenes

These genes are involved in signal transduction, and some are involved in the various phases of the cell cycle. Mutations in cell-cycle regulation or signal transduction can "push" the cell into dividing rapidly and without regard to its surroundings. Over 100 oncogenes have been identified so far. They include genes such as ABL1 (Abelson murine strain leukemia viral homolog) and EGFR (Epidermal Growth Factor Receptor).

Tumor Suppressor Genes

These genes inhibit cell division, working in a manner opposite to that of the oncogenes. Surrounding cells secrete growth-inhibitory signals that help prevent proliferation. These growth-inhibitory signals work in conjunction with tumor suppressor genes. If a tumor suppressor gene is mutated, proliferating cells can ignore these inhibitory messages. This group includes the genes p53, BRCA1, and BRCA2.

Dna Repair Genes

These are the genes that provide the cell with the ability to sense and correct damage to the DNA. Damage to the DNA can be caused by radiation, chemicals, ultraviolet light, or errors in transcription. If these errors are not corrected, they accumulate in the genome and can quickly increase the chance that a cell will become cancerous. Repair genes include those in the DNA-ligase and excision-repair gene families.

Genes Involved in Cell Mortality

A normal cell can only undergo about forty divisions, after which it dies or enters senescence. If a tumor had this limitation it would be very limited in its size, as it would reach its forty divisions relatively quickly. This process is controlled by the enzyme telomerase, which maintains the telomeres (repetitive DNA sequences at the ends of chromosomes that shorten after each round of DNA replication, until they reach a length that causes the cell to die) by not allowing them to shorten. Some cancer cells become immortal as a result of mutations in the telomerase gene, causing the telomeres to be extended indefinitely, allowing the cell to continue dividing without limit. Other mutations affect the process of apoptosis.

Cancer does not usually arise by a single event. Instead, two or more "hits" are needed to convert a well-regulated cell to a cancer cell. This is the case because each cell contains two copies of each gene, one inherited from each parent. Most cancer-causing mutations cause a loss of function in the mutated gene. Often, having only one functional copy is enough to prevent disease. Thus, two mutations are needed.

This can be illustrated by looking at retinoblastoma, a common cancer of the retina. The affected gene (called the retinoblastoma gene) is a tumor suppressor. Spontaneous mutations are rare, but since there are many millions of cells in the retina, several will develop the appropriate gene mutation over the course of a lifetime. It would be very unlikely, though, for a single cell to develop two spontaneous mutations (at least in the absence of prolonged exposure to carcinogens), and thus spontaneous retinoblastoma is very rare.

If, however, a person inherits one copy of an already-mutated gene from one parent, every cell in the eye starts life with one "hit." The chances are very high that several cells will suffer another hit sometime during their life, and so the chances are very high that the person will develop retinoblastoma. Since inheriting a single copy of the mutated gene is so likely to lead to the disease, the gene is said to show a dominant inheritance pattern.

Future Directions in Diagnosis and Treatment

The increased knowledge of cancer at the biochemical and genetic level has led to many advances toward better diagnosis and treatment of cancer, including the design of more specific drugs that are less toxic to normal tissue. This includes the use of antisense molecules, which are nucleic acid sequences that are complementary to the mRNA of a target gene. As the two sequences are complementary, they anneal and thus the mRNA is blocked from being translated into a protein, resulting in less of that particular protein being produced (such as growth factor receptors). Drugs specific in blocking angiogenesis are able to control the growth and spread of tumors, especially when used in combination with other treatments.

Bibliography

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Weinberg, R. A. One Renegade Cell: How Cancer Begins. New York: Basic Books, 1999.

—Giles Watts

A group of diseases characterized by uncontrolled growth of abnormal cells, which have the ability to spread through the body or body parts. Several studies have shown that physically active people are less likely than those who have sedentary lifestyles to develop certain types of cancer (e.g. breast and colon cancer).

Cancer remains one of the most feared diseases of our times. Every year 500,000 Americans die from tumors of one sort or another, up from about 30,000 at the beginning of the twentieth century. Part of the increase is due to population growth and the fact that people now live longer—and cancer is, generally speaking, a disease of the elderly. A smaller fraction of the increase is due to the fact that previously undetected cancers are now more likely to be diagnosed. But cancer risks have also grown over time, due to increased exposures to carcinogenic agents—notably New carcinogens in food, air, and water, such as pesticides and asbestos; the explosive growth of tobacco use in the form of cigarettes, which were not widely used until World War I; and exposure to various forms of radiation, such as X-rays and radioisotopes. Tobacco alone still causes nearly a third of all American cancer deaths—including 90 percent of all lung tumors—making it the single most important cause of preventable cancers.

Cancer is actually a cluster of several different diseases, affecting different parts of the body and different kinds of tissue. Leukemia is a cancer of the blood, myeloma a cancer of the bone marrow, melanoma a cancer of the skin, and so forth. Cancer can be seen as "normal" tissue growing out of control or in places where it should not. In the case of breast cancer, for example, the danger is not from cancer cells confined to the breast, but rather from cancerous breast cells spreading to other parts of the body ("metastasis"), where they grow and eventually interfere with other parts of normal bodily function. Cancerous growths seem to begin when the body's normal cellular "suicide" functions break down; malignant cells are immortal in the sense that they continue to divide instead of periodically dying off as healthy cells should.

A great deal of research has gone into exploring the genetic mechanisms of carcinogenesis, with the hope of finding a way to halt the growth of cancerous cells. The difficulty has been that cancer cells look very much like normal cells, the difference typically being only a few minor mutations that give the cell novel properties. That is why cancer is so difficult to treat. It is not like the flu or malaria, where a living virus or bacterium has infected the body. Cancer cells are often not even recognized as foreign by the body's immune system—which is why they can grow to the point that normal physiological processes are obstructed, causing disability and, all too often, death.

Cancer also has to be understood as a historical disease, since the kinds of cancer that are common in a society will often depend on what people eat or drink, what kinds of jobs or hobbies or habits are popular, what kinds of environmental regulations are enforced, the environ-mental ethics of business leaders and labor activists, and many other things as well. Cancer is a cultural and political disease in this sense—but also in the sense that different societies (or different people within the same society) can suffer from very different kinds and rates of cancer.

Stomach cancer was the number one cause of cancer death in America in the early years of the twentieth century, for example, accounting for about half of all American cancer deaths. By the 1960s, however, stomach cancer had fallen to fifth place in the ranks of cancer killers, as a result of food refrigeration and the lowered consumption of high-salt, chemically colored, and poorly preserved foods. Cancers of the lung, breast, and ovary are now the more common causes of death for women, as are cancers of the lung, colon, prostate, and pancreas among men. Lung cancer has become the leading cause of cancer death among both men and women, in consequence of the rapid growth of smoking in the middle decades of the twentieth century. The twenty-to thirty-year time lag between exposure and death for most cancers explains why the decline of smoking in the 1970s and 1980s only began to show up at the end of the century in falling lung cancer rates.

It is important to distinguish cancer mortality (death rates) from cancer incidence (the rates at which cancers appear in the population). Some cancers are fairly common—they have a high incidence—but do not figure prominently in cancer mortality. Cancer of the skin, for example, is the most common cancer among both men and women, but since few people die from this ailment, it does not rank high in the mortality tables. Most skin cancers are quite easily removed by simple surgery. Lung cancer survival rates, by contrast, are quite low. Mortality rates are tragically close to incidence rates for this particular illness.

Worries over growing cancer rates led President Richard Nixon to declare a "war on cancer" in his State of the Union address of 1971. Funding for cancer research has increased dramatically since then, with over $35 billion having been spent by the National Cancer Institute alone. Cancer activists have also spurred increased attention to the disease, most notably breast cancer activists in the 1980s and prostate cancer activists in the 1990s. Attention was also drawn to Kaposi's sarcoma from its association with AIDS. Cancer researchers have discovered a number of genes that seem to predispose certain individuals to certain kinds of cancer; there are hopes that New therapies may emerge from such studies, though such knowledge as has been gained has been hard to translate into practical therapies. Childhood leukemia is one case where effective therapies have been developed; the disease is now no longer the death sentence it once was. From the point of view of both policy and personal behavior, however, most experts agree that preventing cancer is in principle easier than treating it. Effective prevention often requires changing deeply ingrained personal habits or industrial practices, which is why most attention is still focused on therapy rather than on prevention.

We already know enough to be able to prevent about half of all cancers. The problem has been that powerful economic interests continue to profit from the sale of carcinogenic agents—like tobacco. With heart disease rates declining, cancer will likely become the number one cause of American deaths by the year 2010 or 2020. Global cancer rates are rapidly approaching those of the industrialized world, largely as a result of the increasing consumption of cigarettes, which many governments use to generate tax revenue. The United States also contributes substantially to this global cancer epidemic, since it is the world's largest exporter of tobacco products. Only about two-thirds of the tobacco grown in the United States is actually smoked in the United States; the remainder is exported to Africa, Europe, Asia, and other parts of the world. Cancer must therefore be regarded as a global disease, with deep and difficult political roots. Barring a dramatic cure, effective control of cancer will probably not come until these political causes are taken seriously.

Bibliography

Epstein, Samuel S. The Politics of Cancer Revisited. Fremont Center, N.Y.: East Ridge Press, 1998.

Patterson, James T. The Dread Disease: Cancer and Modern American Culture. Cambridge, Mass.: Harvard University Press, 1987.

Proctor, Robert N. Cancer Wars: How Politics Shapes What We Know and Don't Know About Cancer. New York: Basic Books, 1995.

—Robert N. Proctor

KEY TERMS Benign—Mild, does not threaten health or life. When referring to a tumor, it generally means noncancerous. Malignant—Unfavorable, tending to produce deterioration or death. For a tumor, it generally means cancerous. Radiopharmaceutical—A drug that is radioactive. It is used for diagnosing or treating diseases.

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What is Cancer?

Cancer is a group of diseases characterized by uncontrolled growth of cells in the human body and the ability of these cells to travel from the original site and spread to distant sites. Another name for cancer cells is malignant cells. Diet and nutrition play an important role in cancer prevention and cancer treatment.

Description of Cancer

By definition, cancer is a disease of the genes. A gene is a small part of DNA, which is the master molecule of the cell. Genes make proteins, which serve as the workhorses of the body’s cells. These proteins allow the body to carry out all of the many processes that permit breathing, thinking, moving, and others often taken for granted.

Throughout people’s lives, the cells in their bodies are growing, dividing, and replacing themselves. Many genes produce proteins that are involved in controlling the processes of cell growth and division. Any alteration, or mutation, to the DNA molecule can disrupt the genes and produce faulty proteins. This causes the cell to become abnormal and lose the restraints on its growth. The abnormal cell will begin to divide uncontrollably. The new growth it forms will be called a tumor or neoplasm. Not all tumors are cancerous. Those that are cancerous spread to other parts of the body near the original cancer site or to distant sites. Cancerous tumors are called malignancies. A tumor that is not cancerous is called benign.

Cancer can occur in anyone and is the second leading cause of death in the United States. Although cancer may be inherited, it also may occur due to certain environmental risk factors or behaviors. For example, it is well known that smoking can lead to lung cancer or that unprotected sun exposure is a risk factor for skin cancer. Diet and physical activity also play a role in cancer risk.

Most prevalent cancer-related deaths, 2002.

Male cancers	Deaths	Female cancers	Deaths (000)
Trachea/brounchus/lung	886	Breast Trache/	474
Stomach	523	bronchus/lung	353
Liver	428	Stomach	326
Colon/rectum	321	Colon/rectum	299
Oesophagus	284	Cervix Uteri	239
Prostate	268	Liver	191

The World Health Repor 2003.

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A disease characterized by rapid growth of cells in the body, often in the form of a tumor. Cancer is invasive — that is, it can spread to surrounding tissues. Although this disease is a leading cause of death in the United States, research has provided considerable insight into its many causes (which may include diet, viruses, or environmental factors) and options for treatment (which include radiation, chemotherapy, surgery, and possibly gene therapy).

The term cancer is often used to describe a nonmedical condition that is undesirable, destructive, and invasive: “Watergate was a cancer on the presidency.”

Quotes:

"We need cancer because, by the very fact of its insurability, it makes all other diseases, however virulent, not cancer." - Gilbert Adair

"Nobody knows what the cause is, though some pretend they do; it like some hidden assassin waiting to strike at you. Childless women get it, and men when they retire; it as if there had to be some outlet for their foiled creative fire." - W. H. Auden

"My veins are filled, once a week with a Neapolitan carpet cleaner distilled from the Adriatic and I am as bald as an egg. However I still get around and am mean to cats." - John Cheever

"I don't think makeup is rocket science or a cure for cancer." - Cindy Crawford

"I wish I had the voice of Homer to sing of rectal carcinoma." - John B. S. Haldane

"Cancer patients are lied to, not just because the disease is (or is thought to be) a death sentence, but because it is felt to be obscene -- in the original meaning of that word: ill-omened, abominable, repugnant to the senses." - Susan Sontag

See more famous quotes about Cancer

any malignant neoplasm. Cancers are usually divided into carcinomas, derived from epithelial tissue, and sarcomas, derived from connective tissue. Some 300 genes are known to be involved in carcinogenesis. See APC, BRCA, retinoblastoma, Wilms' tumour.

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Any malignant, cellular tumor.
The term cancer encompasses a group of neoplastic diseases in which there is a transformation of normal body cells into malignant ones. This probably involves some change in the genetic material of the cells, deoxyribonucleic acid (DNA), perhaps as a result of faulty repair of damage to the cell caused by carcinogenic agents or ionizing radiation. The altered cells pass on inappropriate genetic information to their progeny cells and begin to proliferate in an abnormal and destructive way. Normally, the cells of which body tissues are made are regularly replaced by new growth, which stops when the cells are replaced; new cells form to repair tissue damage and stop forming when healing is complete. Why they stop forming is unknown, but clearly the body in its normal processes regulates cell growth. In cancer, cell growth is unregulated.
As the cancer cells continue to proliferate, the mass of abnormal tissue that they form enlarges, ulcerates, and begins to shed cells that spread the disease locally or to distant sites. This migration is called metastasis. Some cells invade neighboring tissues, destroying and displacing normal cells and taking their place. Others can enter the blood and lymphatic vessels and are carried along in the fluid to other parts of the body. Another way in which malignancy can be spread is by entering a body cavity by diffusion and coming in contact with a healthy organ.
See also tumor, neoplasm, neoplasia. For individual cancers see under specific types. Cancers of specific organs or tissues are not listed.

For a list of words related to cancer, see:

• Diseases and Infestations - cancer: malignant tumor anywhere in body due to uncontrolled cell division, causing disruption of metabolism and invasion and destruction of neighboring tissue
• Morality or Character

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See words rhyming with "cancerous."

This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)

Dansk (Danish)
n. - kræft, Krebsen

Nederlands (Dutch)
kanker, Kreeft

Français (French)
n. - (Méd, fig) cancer

Deutsch (German)
n. - Krebs

Ελληνική (Greek)
n. - (παθολ.) καρκίνος, (αστρον.) (ο) Καρκίνος, (μτφ.) καρκίνωμα

Italiano (Italian)
cancro

Português (Portuguese)
n. - câncer (m) (Med.), Câncer (m) (Astron.), caranguejo (m)

Русский (Russian)
рак, язва

Español (Spanish)
n. - cáncer

Svenska (Swedish)
n. - cancer, Kräftan

中文（简体）(Chinese (Simplified))
癌, 恶性肿瘤, 弊端, 病根, 痼疾, 癌症, 巨蟹星座

中文（繁體）(Chinese (Traditional))
n. - 癌, 惡性腫瘤, 弊端, 病根, 痼疾, 癌症, 巨蟹星座

한국어 (Korean)
n. - 암, 사회의 병폐, 하늘의 게자리

日本語 (Japanese)
n. - 癌, 積弊, 蟹座, 蟹座生まれの人
v. - 癌のようにむしばむ

العربيه (Arabic)
‏(الاسم) سرطان‏

עברית (Hebrew)
n. - ‮סרטן, מזל סרטן, השפעה רעה או שחיתות המתפשטות ללא הגבלה‬

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