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Radiation exposures at an early age: impact of genotype on breast cancer risk


The relative risks of breast cancer for women exposed to external radiation in childhood, adolescence and early reproductive years are among the highest known radiation related risks for any cancer type. A number of genes increase breast cancer susceptibility and are known to be involved in detection and repair of radiation-induced DNA damage. DNA repair mechanisms play an important role in the cellular response to radiation exposure and hence on the risk of radiation induced cancer. Mutations or polymorphisms in these genes may therefore render cells more sensitive to radiation-induced cancer. The overall objective of the current contract is to conduct an epidemiological study designed to examine the role of low dose radiation exposure in the aetiology of breast cancer in young women and study its possible interaction with genetic susceptibility. A supplementary objective will be to study the possible modifying effects of other other risk factors for breast cancer, including reproductive factors and cancer therapies other than radiation. Because of the low prevalence of mutation carriers and because of the generally low levels of ionising radiation exposure in the general population, population-based studies of breast cancer risk are unlikely to be informative for this purpose. The current project therefore focuses on the conduct of complementary multi-national nested case-control studies of breast cancer in different populations chosen on the basis of high prevalence of radiation exposure and/or high prevalence of known mutations in susceptibility genes to maximize the power to study the effects of radiation exposure on the risk of breast cancer and its interaction with relatively rare genetic mutations. Overall, it is estimated that approximately 1000 cases of breast cancer and their matched controls from 8 European countries will be included in the case-control studies.

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150 Cours Albert Thomas

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