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||BREAST CANCER RISK POLYMORPHISMS AND INTERACTION WITH IONIZING RADIATION AMONG U.S. RADIOLOGIC TECHNOLOGISTS in: Abstracts of the 41st Annual Meeting of the Society for Epidemiologic Research
||Bhatti P, Doody MM, Alexander BH, Y J, Simon SL, Weinstock RM, Rosenstein M, Stovall M, Abend M, Preston DL, Struewing JP, Sigurdson AJ
||Am J Epidemiol
||2008 Jun 1
||Genome-wide association studies are discovering relationships betweensingle nucleotide polymorphisms (SNPs) and breast cancer, but the functionsof some SNPs are obscure. Examining these SNPs in conjunction withenvironmental exposures may help elucidate SNP function, but more importantly,identify subgroups with genetic backgrounds that are particularlysensitive to environmental exposures. We tested eleven variants, initiallyidentified for confirmatory genotyping by the Breast Cancer AssociationConsortium, for gene-radiation interaction among 859 breast cancer casesand 1083 controls that were occupationally exposed to ionizing radiationand are nested within the U.S. Radiologic Technologists cohort. Ionizingradiation is an established breast cancer carcinogen and has been previouslyassociated with breast cancer risk in this cohort. To evaluate SNP-radiationeffect modification, we assessed the heterogeneity of occupational radiation-related excess odds ratios across SNP genotypes using likelihood ratiotests. All regression models were adjusted for year of birth and includedradiation exposure from personal diagnostic examinations. We found thatthe radiation-associated breast cancer risk varied significantly by genotypefor rs2107425 in the H19 gene (pinteraction = 0.005). Further testing of theH19 gene and the rs2107425 variant in biologically-based radiation assaysmay illuminate possible functional relevance for this gene in directly affectingcellular control of radiation-induced damage, apoptosis, or proliferationor by epigenetic mechanisms.