Cancer of the breast is the most common major cancer among women in the United States, and the incidence rate of female breast cancer has been increasing in the United States and in many other areas of the world. In Connecticut, the incidence rate of female breast cancer has been increasing during the past several decades, particularly in women age 50 and over. While considerable efforts have been made, little is known about the etiology of breast cancer and the factors which might be responsible for the observed time trends. Recent epidemiologic studies strongly suggest that environmental exposure to organochlorine residues increases the risk of female breast cancer. This association is biologically plausible. Many organochlorine compounds are known animal carcinogens, suspected human carcinogens, have tumor promotion activity, possess estrogenic activity, and may compromise immune function. Due to the inconclusive nature of the recent epidemiologic studies (small numbers of subjects, lack of control for all potential confounders) and the widespread exposure to organochlorine compounds, there exists an urgent need for more rigorous epidemiologic studies. Against this background, a case-control study of organochlorine compound exposure and risk of breast cancer in Connecticut is proposed. More specifically, this study will test the hypotheses that a) exposure to total polychlorinated biphenyls (PCBs) and specific major PCB congeners increases the risk of female breast cancer; b) exposure to DDT and its most stable and persistent metabolite DDE increases the risk of female breast cancer; and c) exposure to benzene hexachloride (BHC) isomers, particularly alpha-, beta- and gamma-BHC, increases the risk of female breast cancer. Cases and controls will be patients diagnosed over a three and one-quarter year period at the Yale- New Haven Hospital. The case group will consist of 200 incident primary breast cancer patients with in situ or stage I-III disease. An equal number of controls will be selected from women who are diagnosed with benign breast disease (excluding atypical hyperplasia). Cases and controls will be between ages 50 and 79 and will have sufficient non-diagnostic breast adipose tissue for chemical analysis. The concentration of organochlorine compounds in breast adipose tissue will be analyzed by gas chromatography and compared between the cases and controls. Subsequent to tissue collection, cases and controls will be interviewed in their homes by trained interviewers using a standardized, structured questionnaire to obtain information regarding potential confounding factors, including age, lactation history, body mass index, dietary intakes, exposure to non- organochlorine pesticides, and reproductive history. Statistical analyses will be performed using standard multivariable techniques to address the study hypotheses and to control for confounding.
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