CancerNet from the National Cancer Institute ****************************************************************************** * CANCER FACTS * * National Cancer Institute * * National Institutes of Health * ****************************************************************************** Highlights of NCI's Carcinogenesis Studies Prevention is a key component and current priority of the National Cancer Institute (NCI) in its mission to reduce death and suffering from cancer. As part of the large-scale effort to prevent cancer, NCI has a multifaceted research program to identify cancer-causing agents (carcinogens) and their relationship to cancer risk. These studies are designed to: - Identify the chemical, physical, and biological substances that cause or promote cancer; - Determine the ways in which cancer-causing agents are activated in the body; - Discover how the activated carcinogens cause damage to cells (gene mutations and chromosome alterations); - Study the changes that occur in the cell at each step of the cancer process; and - Determine the reasons for increased cancer susceptibility in certain families and in persons exposed to substances through occupation and other activities. Ultimately, NCI uses this information to develop measures and agents to reverse, interrupt, or prevent cancer before clinical disease develops. The NCI is one of the major Federal agencies that develops the research base for the regulatory agencies of the U.S. Government to do their jobs. For example, NCI research on industrial pollutants, pesticides (such as 2,4-D), radon, electromagnetic fields, secondhand tobacco smoke, and many other known and potential carcinogens serves as the basis for regulatory actions taken by the U.S. Environmental Protection Agency (EPA), the Occupational Safety and Health Administration, the Consumer Products Safety Commission, and the U.S. Food and Drug Administration. These agencies monitor and regulate the amount of contaminants found in the environment and at worksites, while NCI, whose primary mission is research, conducts certain studies that identify cancer-causing agents requiring protective regulation or education programs. The NCI works closely with a sister component of the National Institutes of Health, the National Institute of Environmental Health Sciences (NIEHS), as well as with the Centers for Disease Control and Prevention (CDC). The NIEHS currently directs the National Toxicology Program, which identifies chemicals as carcinogens through extensive laboratory and animal testing. This program began as part of NCI, but was transferred to a separate program in order to also test for toxicities other than cancer. The NCI continues to make recommendations for chemicals to be tested through the program. BASIC CARCINOGENESIS RESEARCH Laboratory research supported by NCI is aimed at increasing our understanding of the cellular and molecular changes involved in cancer caused by chemical agents, by physical agents such as radiation, or by biological agents such as viruses. Carcinogenesis is considered a multistep process in which several events are required to produce cancer; initiation, promotion, and progression steps have been identified. The ability to distinguish between these steps and analyze them is possible through specialized research on molecular and cellular biology and on carcinogen metabolism. Special emphasis is being placed on studies of the effects of carcinogens on cell structure and function, as well as studies of compounds that may promote cancer, such as growth factors and hormones. Research targeting carcinogen metabolism, DNA damage, DNA repair, activation of oncogenes by chemical carcinogens, and development of new chemopreventive agents and preventive strategies is actively being pursued. Viruses are also environmental agents with potentially carcinogenic effects. In fact, cancer research has found strong links between specific viruses and various cancers. Newly developed laboratory techniques are being used to evaluate how cancer-causing viruses insert themselves into genes. RNA viruses such as HIV-1, the cause of AIDS; HTLV-1 and HTLV-II, which cause rare leukemias; DNA viruses such as hepatitis B and C, which greatly increase the likelihood of developing liver cancer; and papillomavirus, the leading factor of cervical cancer, are the subjects of many studies. These viruses provide tools for understanding how cellular genes and their products change a normal cell into a cancer cell. Other studies are focused on oncogenes, tumor suppressor genes ("anti-oncogenes"), growth factors, and other molecular level components of the cancer process. The ability of cancer cells to grow under conditions that normally would stop or slow cell growth is related to the changes these viruses and proteins initiate. Any of the genetic changes that change cell functions may initiate cancer. EPIDEMIOLOGIC RESEARCH Epidemiologic studies of human populations are performed to identify environ- mental, occupational, familial, and other risk factors predisposing to various cancers. The NCI studies the natural history of cancer in humans, and looks at the incidence of cancers in different geographic locations to help identify causal association of risk factors to various cancers. The relative contribution of environment, lifestyle, and host determinants to the human cancer burden are being studied, with special emphasis placed on studies aimed at understanding the high rates of certain cancers in blacks and other minority groups. These epidemiologic studies are essential to NCI's vigorous prevention program. In view of the increasing importance of nutrition and lifestyle in the causation or prevention of cancer, projects on dietary mutagens and carcinogens, alcohol consumption, and tobacco use are also emphasized. Many studies deal with the presence of mutagens (substances which damage DNA), carcinogens, and natural anticarcinogens in foods. Other studies assess the carcinogenic effects of smokeless tobacco and passive smoking. A significant focus of activities is the assessment of environmental contaminants such as pesticides as risk factors for human cancer. Occupational Carcinogens As part of the epidemiologic research to determine potential carcinogens, NCI has had a long-term commitment to studies of cancer hazards and their abatement. For example, NCI-supported studies were among the first to quantify the hazards of asbestos exposure in the workplace; in the late 1970s, NCI conducted a nationwide asbestos awareness campaign for the public and health professionals. Studies are under way to determine the occupation-related cancer risk for farmers, firefighters, plumbers and pipefitters, lawncare workers and pesticide applicators, chemists, miners, shipyard workers, migrant and seasonal farm workers, and potters, to name a few. These individuals are exposed to potentially harmful chemicals, dusts, and air pollutants on the job. By studying the health effects of concentrated exposures to these substances, researchers not only find ways to reduce harmful risks for these individuals, but also will be better able to study the potential effects from exposure to a low concentration of these substances. Studies on farmers and their exposures to herbicides are a critical example of this type of research. In the 1980s, NCI began several studies comparing pesticide use by farmers with cancer to those without the disease and found that farmers who used herbicides, especially 2,4-D (2,4-dichlorophenoxyacetic acid), had an excess of non-Hodgkin's lymphoma as compared to those who did not use the weedkiller. This year, with EPA and NIEHS, NCI began a massive study of 100,000 farmers and their family members to try to determine reasons for their elevated risk of cancers of the brain, prostate, stomach, skin, and lip, as well as leukemia, multiple myeloma, and non-Hodgkin's lymphoma. Farmers have chronic exposures to potentially harmful compounds such as pesticides (insecticides, fungicides, rodenticides, herbicides, and others), chemical solvents, engine exhaust, animal viruses, sunlight, and other substances common to agriculture. Environmental Carcinogens In studies related to and stemming from the research on farmers, scientists have assessed the health effects of exposure to the defoliant Agent Orange during the Vietnam War, and have also determined that there is an increased risk for cancer in dogs routinely exposed to herbicides used by their owners. The health effects of other unintentional exposures to chemicals are being tracked by NCI. For example, in the mid-1970s, contamination of animal feed with PBBs (polybromated biphenyls) on about 600 farms in Michigan led to widespread contamination of farm animals, milk, and residents in the area. Since 1978, NCI has been collaborating with CDC, NIEHS, and the Michigan Department of Public Health to monitor the health effects of this exposure and to collect blood samples from the 4,000 residents with the highest exposures. These people are being evaluated in several case-control studies, including one in which the researchers will compare the levels of PBB residues in breast fat of women who are diagnosed with breast cancer to the level of residues in women without breast cancer. Another group of individuals exposed from about 1947 to 1971 to high levels of the now-banned pesticide DDT (dichlorodiphenyltrichloroethane, an organochlorine pesticide) live in a rural area in Alabama. During that time, a chemical company discharged tons of DDT waste into a nearby river where the residents regularly caught fish for their families' meals. This exposure was discovered in 1979, which led CDC to investigate. The CDC found that blood levels of DDE, a metabolite of DDT, were 10 times higher in this group than the national average. This group is under medical surveillance, and a health survey is being completed for all residents in the area. The NCI is planning to utilize the survey results in developing a case-control study to compare DDE residues in breast fat of women with breast cancer to residues in women without breast cancer. In collaboration with the University of Alabama School of Nursing, NCI is developing a screening mammography program for the residents. In a highly polluted area of China, NCI has been conducting studies on how air pollution affects lung cancer risk. In addition to an increased risk from smoking cigarettes and other tobacco products, NCI researchers found increased risk for people who reported that the outdoor environment where they lived was smoky. Residents living within 200 meters of copper smelters were exposed to arsenic and had a greatly increased risk of lung cancer, confirming results of an earlier study carried out in Montana. NCI researchers also found that indoor air pollution from coal-burning stoves and cooking oils increased risk for the disease. Radiation Risks The cancer risks associated with all types of radiation are also under heavy scrutiny. Indoor radon exposure has received considerable study, and it now appears to be less of a cancer threat than once feared. NCI epidemiologists looked at cancer deaths in populations living around nuclear facilities and found no increased risk due to living near such facilities. NCI researchers have found that radiation treatment for breast cancer contributes very little to the risk of developing a new cancer in the opposite breast. In a study of 41,000 women diagnosed with breast cancer between 1935 and 1982, fewer than 3 percent of the second primary breast cancers that occurred could be attributed to radiation therapy administered 5 or more years previously. However, another study showed that certain drug and radiation therapies used to treat breast cancer patients in the 1970s and early 1980s increased the patients' risk of developing leukemia. In a study of women diagnosed with breast cancer between 1973 and 1985, the overall subsequent occurrence of leukemia was lowþonly 90 of 82,700 women developed the disease (about 1 in 1,000 women). However, this rate was higher than expected, and leukemia risk varied depending on the type and amount of drugs received, the amount of radiation used, and whether or not these treatments were given at the same time. Using information from an earlier NCI study of over 100,000 female radiological technologists, exposure to radiation on the job is being evaluated as a risk factor for breast and thyroid cancer. Over 5,000 women exposed to multiple diagnostic x-rays to monitor treatments for curvature of the spine are also being examined to clarify the risk of radiation-induced breast cancer. A large-scale study is under way to examine whether exposure to electromagnetic radiation from electric power lines is linked to the development of childhood leukemia. This study is part of a larger investigation by the Children's Cancer Group to evaluate the risk of acute lymphocytic leukemia associated with a wide range of factors, such as prenatal x-rays, childhood and maternal diseases, maternal drug use, maternal smoking, parental occupations, household chemical exposures, and family genetic histories. Another NCI-sponsored study launched recently because of a public health alarm will look at brain cancer risks associated with the use of cellular and other telephones. COMMUNICATIONS AND OUTREACH An important part of NCI's mission is to provide information to cancer patients and their families, health professionals, and the public-at-large about cancer prevention, detection, and treatment issues. Through the toll- free number of the Cancer Information Service (1-800-4-CANCER), the free distribution of publications, worksite health promotion interventions, and nationwide antismoking activities, NCI actively seeks to provide information to all Americans about environmental cancer risks, and stresses the ways in which cancer risk can be reduced by avoiding exposures to known carcinogens. The NCI has always been a major supporter of international reports that identify carcinogens worldwide. Attached is a list of occupational groups and industries, and environmental agents under study. # # # The Cancer Information Service (CIS), a program of the National Cancer Institute, is a nationwide telephone service for cancer patients and their families, the public, and health care professionals. CIS information specialists have extensive training in providing up-to-date and understandable information about cancer. They can answer questions in English and Spanish and can send free printed material. In addition, CIS offices serve specific geographic areas and have information about cancer-related services and resources in their region. The toll-free number of the CIS is 1-800-4-CANCER (1-800-422-6237). OCCUPATIONAL GROUPS AND INDUSTRIES PREVIOUSLY OR CURRENTLY UNDER STUDY Acrylonitrile workers Iron and Iron-steel workers Agricultural workers Jewelry workers Aircraft maintenance workers Laboratory workers Artistic painters Metal polishers and platers Beauticians Miners (tin, uranium, and others) Benzene and Benzidine workers Nuclear power plant workers Ceramic fixture workers Oil refinery workers Chemists and pharmaceutical workers Pesticide applicators Chromate pigment workers Photographers and photographic film makers Coast Guard marine inspectors Pipefitters and plumbers Copper smelter workers Plastic resin workers County extension agents Pottery workers Dry cleaners Quartz workers Dusty traders with silica exposure Radiologists Embalmers Shipyard workers Farmers Textile workers Firefighters Truck drivers Forestry and soil conservation Veterinarians Formaldehyde workers Welders Furniture workers X-ray technologists Grain handlers Zinc chromate painters Herbicide applicators ENVIRONMENTAL AGENTS UNDER STUDY Air Pollution - Indoor Air Pollution - Outdoor Cooking oil vapors Diesel exhaust Environmental tobacco smoke Gasoline exhaust Polycyclic aromatic hydrocarbons Motor exhaust emissions Radon Polycyclic aromatic hydrocarbons Smelter emissions Dusts Arsenic Cadmium Cotton dusts Chromium Grain dusts Lead Organic dusts Nickel Plastic dusts Zinc Textile dusts Wood dusts Heterocyclic aromatic amines IQ (2-amino-3-methylimidazo[4,5-f]quinoline) MeIQx (2-amino-3,8-methylimidazo[4,5-f]quinoxaline) PhIP (2-amino-1-methyl-6-phenylimidaxo[4,5,b]pyridine) Organic Solvents Insecticides Herbicides Benzene Carbamates Acetamides Carbon tetrachloride Carbaryl Popachlor Methylene chloride Carbofuran Benzoic acids Tetrachloroethylene Chlorinated hydrocarbons Chloramben Toluene Aldrin Heptachlor Dicamba Trichloroethylene Chlordane Lindane Dinitroanilines Xylene DDT Toxaphene Trifluralin Organophosphates Phenoxyacetic acids Diazinon 2,4-D Dichlorvos 2,4,5-T Malathion Triazines Phorate Atrazine Terbufos Cyanazine Polybrominated biphenyls Polychlorinated biphenyls Fumigants Water Pollution Ethylene dibromide Arsenic Ethylene dichloride Chloride and chlorination byproducts Phosphene (includes chloroform and other trihalomethanes) Fluoride Petroleum Products Nitrates Pesticides Diesel fuel Gasoline Drugs Jet fuel Oils P-Aminosalicytic acid Amphetamines Anticonvulsive drugs Dilantin Phenobarbital Radiation Biological Agents Ionizing Chlamydia Indoor radon Epstein-Barr Virus Neutron therapy Helicobacter pylori Reactor accident (Chernobyl) contamination Hepatitis-B and -C virus Radioisotopes Herpes simplex virus Iodine-131 types 1, 2, 6, and 7 Radium-224 HIV-1 and -2 Thorotrast HTLV-I and II X-rays Human papillomavirus Nonionizing Electromagnetic fields Ultraviolet Date Last Modified: 6/93 .