Environmental Factors and Breast Cancer Risk For millions of women whose lives have been affected by breast cancer, the 1994 discovery of the first breast cancer gene by researchers from the National Institute of Environmental Health Sciences (NIEHS) was a welcome sign of progress in the fight against this dreaded disease. While this discovery and others like it are certainly encouraging, statistics tell us that breast cancer is still a major health concern for women everywhere. According to the American Cancer Society, more woman’s chances of developing interplay between genetics and the women in the United States are breast cancer, they do not yet know environment in the development living with breast cancer than how these risk factors work together of this disease. The Sister Study with any other non-skin cancer. to cause normal cells to become is enrolling 50,000 healthy sisters Breast cancer is the leading cause cancerous. Most experts agree of women diagnosed with breast of cancer death for U.S. women that breast cancer is caused by a cancer from across the country. between the ages of 20 and 59, combination of genetic, hormonal Women of all backgrounds and and the leading cause of cancer and environmental factors. ethnic groups who are between death for women worldwide. 35 and 74 years of age are encouraged to participate. Gene-Environment Interactions Sisters of breast cancer patients For years, NIEHS has played a share many of the same genes, leadership role in funding and conducting studies on the ways are more likely to develop the in which environmental exposures disease themselves, and are likely increase breast cancer risk. These to have been exposed to the same studies have included the use of environmental risk factors during animal models to understand the role of environmental agents in the early childhood. initiation and progression of cancer, The researchers will compare the as well as research on chemical risk The Sister Study genetic profiles and environmental factors and genetic susceptibility As new research continues to exposures of sisters who don’t in human populations. unravel the mysteries surrounding develop breast cancer with those the causes of breast cancer, NIEHS who do become cancer patients Although scientists have identified scientists are laying the groundwork in order to uncover clues that many risk factors that increase a for a landmark study of the possible may ultimately eliminate this dreaded disease. PO BOX 12233 Research Triangle Park, NC 27709 Phone: 919. 541.1919 http://www.niehs.nih.gov January 2007 Study volunteers provide defective, can predispose a woman researchers with samples of their to hereditary breast and ovarian blood, urine, toenail clippings and cancer.1 Diagnostic tests can household dust, each of which will now identify women who have be analyzed for pesticides, heavy inherited defective copies of the metals and other environmental gene and are more likely to chemicals that may be linked to develop breast cancer. breast cancer development. The Although genetics is an important researchers will also look for contributor to breast cancer specific gene variations that may development, twin studies predispose a woman to the effects conducted by scientists in of cancer-causing agents. Women Scandinavia showed that inherited enrolled in the study also fill out factors accounted for only 27 detailed questionnaires about their percent of breast cancer risk.2 health history, past environmental Another study shows that the exposures, and lifestyle. The breast cancer rates of descendants participants will be given yearly of Japanese women who migrate follow-up questionnaires to account to the United States become for changes in their health status or similar to the higher breast cancer environmental exposures. rates of Western women within solvents and flame retardants, and one or two generations.3 These a variety of chemicals used in the findings point to the significant manufacturing of dyes, rubber, role played by environmental vinyl, and polyurethane foams. factors in determining breast cancer susceptibility. Breast Cancer and Environment Research Centers Cancer-Causing Chemicals Recent studies suggest that Scientists are particularly interested exposures to cancer-causing in whether exposure to naturally chemicals during development occurring and synthetic chemicals may affect breast cancer risk later may influence breast cancer in life. During early childhood risk. This includes exposure to and adolescence, the developing Discovery of the BRCA1 Gene chemicals in the air we breathe, breast tissue is composed of the food and beverages we rapidly dividing cells. These The impact of family history on consume, and the chemicals that immature breast cells are much breast cancer risk suggests that come in contact with our skin. more susceptible to the damaging genetic factors play an important The National Toxicology Program, effects of environmental chemicals. role in breast cancer susceptibility. an interagency testing program Results from animal studies have Researchers are just beginning headquartered at the NIEHS, has shown that early exposures to some to understand how changes in listed more than 40 chemicals in chemicals may keep the mammary certain genes can impair the gene’s its Report on Carcinogens because gland in an immature state for ability to control cell growth and they were found to cause tumors in longer periods, increasing its division, causing normal breast laboratory animals. These include susceptibility to chemical insult. cells to become cancerous. In 1994, pharmaceutical products such NIEHS scientists collaborated with as diethylstilbestrol, a synthetic In an effort to uncover the links researchers from the University of form of estrogen that was used between early environmental Utah Medical Center to identify to prevent miscarriages, chemical exposures and cancer risk, NIEHS a gene called BRCA1 that, when is partnering with the National Cancer Institute to fund four Breast and concerns of the breast cancer Researchers at Fox Chase Cancer Cancer and the Environment advocacy community are heard Center are exposing rats to the Research Centers (see text box on last and that the research findings are plasticizers bisphenol A and butyl page). The purpose of the centers disseminated to the public. benzyl phthalate at different is to investigate the impact of times during mammary gland Scientists at the University of prenatal and childhood exposures development. The investigators California, San Francisco have on mammary gland development, are finding that these endocrine found that GATA-3, a gene that and the potential of these exposures disrupting compounds activate guides the development of stem to alter the risk of breast cancer different genes depending on the cells into mature mammary cells, is in later adulthood. The research time of the exposure and the age also required for mammary findings will be developed into at which the rats are examined. cells to remain in the mature state public health messages designed during adulthood. Experiments in Experiments conducted by to educate young women who are mice reveal that without the critical scientists at Michigan State at risk for breast cancer about the gene, mature mammary cells revert University are focusing on the role roles of environmental agents in to a less specialized state that of progesterone, a hormone breast cancer development, and is characteristic of secreted in the the importance of reducing their aggressive breast second half of exposures to these agents. cancer.4 The results the menstrual cycle, Initiated in 2003, the centers have suggest that a in breast cancer worked in close collaboration on defective GATA-3 development. two different approaches to the gene may play a The researchers early exposure hypothesis. One significant role in are using animal approach will use basic science the development models to study techniques in laboratory animals of certain kinds the influence of and cell cultures, while the other of breast cancer. progesterone on will use epidemiologic studies mammary gland At the University in human populations. Each cell growth and of Cincinnati Center, center has a community outreach maturation. The investigators are component to ensure that the views responses they studying the effect get from the animal data may of childhood diet and obesity on shed new light on the role the maturation of the developing of this female hormone in mammary gland and subsequent human breast development. risk of cancer later in life. Their preliminary work with animals Chemical Exposures shows that treatment with soy in Human Populations and other estrogen-like plant compounds may influence In some regions of the country, not only the rate of mammary where there is an unusually gland maturation, but also the high incidence of breast cancer, susceptibility of the gland to environmental factors have been chemical carcinogens. They are targeted as a possible cause for also testing the hypothesis that this increase. During the 1990’s, pre-pubertal obesity in young the NIEHS and the National girls may lead to earlier first Cancer Institute co-funded the menstruation and increased Long Island Breast Cancer Study susceptibility of the mammary Project, one of the largest and gland to carcinogenic insults. most comprehensive studies ever conducted on the environmental Northeast Mid-Atlantic Breast by suppressing the levels of a key Cancer Program, included data hormone called melatonin. The from five separate studies – two study also showed that extended conducted in New York, one in periods of darkness greatly slowed Connecticut, another in Maryland, the growth of these tumors.(8) and the Nurses’ Health Study, The results provide a possible a nationwide investigation into explanation for the higher rate the risk factors for major chronic of breast cancer in female night causes of breast cancer, to diseases in women. In each of the shift workers and the epidemic investigate the high rate of breast studies, blood was drawn from rise in breast cancer incidence in cancer on Long Island in New York. both breast cancer patients and industrialized countries like the healthy controls, and tested for United States. The study scientists focused their DDT, DDE, and polychlorinated investigation on three widespread While these findings are biphenyls. A combined analysis pollutants to which many of encouraging, more research of the data from the five studies the Long Island residents had is needed to pinpoint the revealed no significant association been exposed – organochlorine environmental and genetic factors between the subjects’ serum pesticides, including DDT and its that determine breast cancer concentrations of these compounds metabolite DDE, polychlorinated susceptibility. Once scientists and an increased risk of breast biphenyls, toxic compounds used can identify the elements that cancer.7 in electrical transformers, and are associated with cancer risk, polycyclic aromatic hydrocarbons appropriate interventions and (PAHs), a primary component of precautions can be designed urban air pollution. Although there for those who are most likely was some evidence of a modest to develop the disease. increase in the risk of breast cancer from PAH exposure, the researchers did not identify any environmental NIEHS Breast Cancer and the factors that could be responsible Environment Research Centers for the high incidence of breast cancer in the Long Island area.5 Pursuing New Leads: • Fox Chase Cancer Center, Artificial Light In a separate study conducted on Philadelphia Long Island women, researchers Results from a study conducted • University of California, at Stony Brook University found by NIEHS-funded researchers in San Francisco no association between exposure New York are the first experimental to electromagnetic fields from evidence that artificial light may • Michigan State University, residential power use and breast play an important role in breast East Lansing cancer risk.6 cancer development. The results • University of Cincinnati, show that nighttime exposure A similar NIEHS-NCI funded Cincinnati, Ohio to artificial light stimulated the study of environmental exposures growth of human breast tumors and breast cancer incidence, the 1. Miki et al. (1994) A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1. Science 266(5182):66-71. 2. Lichtenstein et al. (2000) Environmental and Heritable Factors in the Causation of Cancer: Analyses of Cohorts of Twins From Sweden, Denmark and Finland. New England Journal Medicine 343(2):78-85. 3. Shimizu et al. (1991) Cancers of the Prostate and Breast Among Japanese and White Immigrants to Los Angeles County. British Journal Cancer 63:963-966. 4. Kouros-Mehr et al. (2006) GATA-3 Maintains the Differentiation of the Luminal Cell Fate in the Mammary Gland. Cell 127:1041-1055. 5. Gammon et al. (2002) Environmental Toxins and Breast Cancer on Long Island I: Polycyclic Aromatic Hydrocarbon DNA Adducts. Cancer Epidemiology Biomarkers Prev. 11:677-685. 6. Schoenfeld et. al. (2003) Electromagnetic Fields and Breast Cancer on Long Island: A Case-Control Study. American Journal Epidemiology 158(1):47-58. 7. Laden et al. (2001) 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and Polychlorinated Biphenyls and Breast Cancer: Combined Analysis of Five U.S. Studies. Journal National Cancer Institute 93(10):768-775. 8. Blask et al. (2005) Melatonin-Depleted Blood from Premenopausal Women Exposed to Light at Night Stimulates Growth of Human Breast Cancer Xenografts in Nude Rats. Cancer Research 65:11174-11184.
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