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Gene-radiation interactions: their influence on pre-menopausal breast cancer risk after Chernobyl (GENE-RAD-INTERACT), Final report (summary)

Project ID: FIGH-CT-2002-00215
Funded under: FP5-EAECTP C


Breast cancer is the most common cancer and one of the leading causes of death from cancer among women worldwide, with nearly 1 000 000 new cases per year (Globocan, 2000). Known risk factors for breast cancer include genetic susceptibility, reproductive factors, post-menopausal weight, history of benign breast disease, and exposure to ionising radiation (UNSCEAR 2000, Stewart and Kleihues, 2003).
Epidemiological studies of atomic bomb survivors and medically irradiated populations show increased risks of female breast cancer (ranging from 1.1 to 2.7 at 1 Gy) following external irradiation before the age of 40 years (Boice et al., 1996). The relative risks of breast cancer for women exposed to external radiation in childhood and adolescence are substantially higher than for those exposed as adults (Bhatia et al., 1996, Hildreth et al., 1989, Pierce et al., 1996, Thompson et al., 1994, van Leeuwen et al., 2000, van Leeuwen et al., 2003) and are among the highest known radiation-related risks for any cancer type along with leukaemia and thyroid cancer following exposure in childhood (UNSCEAR, 2000).
A number of studies have clearly demonstrated that a fraction (of the order of 12 %) of breast cancer risk is inherited (Goldgar et al. 1994; Lichtenstein et al. 2000; Pharoah et al. 2002; Amundadottir et al. 2004). Several of the genes that play important roles in the response to DNA damage produced by ionising radiation are now implicated as either high-risk or moderate-risk breast cancer susceptibility genes. These include BRCA1, BRCA2, ATM, NBS1, CHEK2, XRCC1 and XRCC3. It is therefore of interest to evaluate the possible joint roles of ionising radiation and genetic susceptibility in the risk of breast cancer.

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