Breast Cancer Risk and Molecular Change After Chernobyl

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DESCRIPTION (provided by applicant): Exposure to ionizing radiation is well documented as a cause of breast cancer in women, but little is known about the effects on breast cancer risk of exposure to radiation at low doses, protracted over time, and the biologic mechanisms responsible for radiation associated breast cancer are poorly understood. Populations exposed to radiation from the Chernobyl accident provide a powerful and unique opportunity to investigate these questions. This study will capitalize on this opportunity and has two primary aims: 1) to investigate whether the risk of premenopausal breast cancer is associated with individual radiation dose to the breast from the Chernobyl accident, to estimate the risk per unit dose, to investigate the shape of the dose- response, and potential dose effect modifying factors, including molecular characteristics and established breast cancer risk factors; and 2) to investigate whether the association of breast cancer risk with radiation exposure differs according to characteristics of breast cancer, including hormone receptor status, genomic loss and gain, and specific alterations in 14 selected DMA repair genes. Premenopausal breast cancer cases diagnosed between 4/1/07 and 9/30/11 who were resident in the Bryansk Oblast of Russia at the time of the Chernobyl accident will be identified and their diagnosis confirmed by an independent panel of experts. Controls will be selected from female residents of the Bryansk Oblast without breast cancer and matched to cases by calendar year of birth and raion of residence on April 26, 1986. For all cases and controls the following will be collected: 1) demographic and personal and family health history; 2) residential and dietary history and 3) a blood sample. Individual radiation dose to the breast will be estimated for each case and control. Fresh breast tumor tissue will be collected for each case for pathology review, immunohistochemistry, and recovery of pure tumor cell samples, and DMA from these cell samples will be extracted for array studies, STR analysis and methylation assays. For cases DMA will be extracted and purified from tissue and blood samples to assess breast cancer characteristics, including hormone receptor status, loss of heterozygosity, gene amplification, and epigenetic gene inactivation, and to estimate the association between these characteristics and individual radiation dose. Gynecological, obstetrical, and clinical information will be collected from cases to assess the distribution of established risk factors for breast cancer in Russian women, including reproductive factors, family history of breast and/or ovarian cancer, hormone use, alcohol consumption, exercise, body mass index, and history of medical irradiation and to investigate their effect on the dose-response relationships assessed in Aims 1 and 2.