Abstract 5618: Polymorphisms in DNA repair genes are associated with endometrial cancer risk among Japanese women

Abstract

Abstract Common polymorphisms in DNA repair genes may affect an individual's capacity to repair damaged DNA. Although many former studies have reported an association between several types of cancers and DNA repair polymorphism, the association with endometrial cancer (EC) risk has not been investigated fully, especially in Asian population. To examine the association between DNA repair polymorphisms and postmenopausal EC risk, we conducted a case-control study with 91 EC cases (59 endometrioid adenocarcinoma and 32 other types of carcinoma) and 261 non-cancer female controls from database of Hospital based Epidemiologic Research Program at Aichi Cancer Center. We examined 16 coding SNPs (single nucleotide polymorphism) of 12 DNA repair genes (OGG1, MUTYH, XRCC1, APE1, ADPRT, XPA, XPC, XPD, ERCC1, RAD23B, XPG, ERCC6) by TaqMan Methods. We surveyed lifestyle/environmental information by self-administered questionnaire. Impact of each SNPs on EC risk was evaluated by multivariate unconditional logistic regression models. Further, we examined the gene-gene interaction. We observed significant association between EC risk and rs1799782 (C>T, Arg194Trp) of XRCC1 [CT: Odds ratio (OR) = 1.74, 95% confidence interval (95% CI) = 0.99-3.04, TT: OR = 2.76, 95% CI = 1.23-6.16; trend p = 0.007]; rs25487 (G>A, Arg399Gln) of XRCC1 [GA: OR = 0.66, 95% CI = 0.39-1.12, AA: OR = 0.15, 95% CI = 0.02-1.16; trend p = 0.019]; rs1136410 (T>C, Val762Ala) of ADPRT [TC: OR = 1.49, 95% CI = 0.84-2.64, CC: OR = 1.92, 95% CI = 0.88-4.18; trend p = 0.076]; and rs17655 (G>C, Asp1104His) of XPG [GC: OR = 0.68, 95% CI = 0.39-1.21, CC: OR = 0.54, 95% CI = 0.26-1.12; trend p = 0.082]. Although both XRCC1 and ADPRT involve in base excision repair, gene-gene interaction of these polymorphisms were not significant; the interaction p between rs1799782 and rs25487 was 0.687; that between rs25487 and rs1136410 was 0.328. In conclusion, we found significant association between EC risk among postmenopausal Japanese women and DNA repair polymorphisms. Gene-gene interactions between XRCC1 and ADPRT were not significant. These results suggests that DNA repair polymorphisms might be associated with etiology of EC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5618. doi:10.1158/1538-7445.AM2011-5618