Abstract 1870: Genotype polymorphisms of DNA repair genes interact with estrogen exposure to breast cancer susceptibility

Abstract

Abstract Endogenous estrogen is suggested to initiate cell proliferation and cause oxidative DNA damage during breast tumorigenesis. Cells eliminate DNA damages by repair enzymes. Genotypic variants of DNA damage repair genes, participating base excision repair (BER) and nucleotide excision repair (NER) pathways, may act as modifiers that affect the association between estrogen exposure and breast cancer. In a hospital-based case-control study of female breast cancer, DNA samples from 401 cases and 533 healthy controls were enrolled among Chinese women in Taiwan. Genotyping polymorphisms of XRCC1 (Arg194Trp and Arg399Gln), OGG1 (Ser326Cys and Arg229Gln), ERCC2 Lys751Gln, ERCC4 Pro662Ser, and ERCC5 His1104Asp were determined and used to evaluate breast cancer susceptibility. Of these non-synonymous polymorphisms, ERCC5 1104Asp variant was significantly associated with breast cancer (OR=1.42; 95%CI=1.08-1.97), and this was more pronounced in women with prolonged estrogen exposure. A trend toward an increased risk of developing breast cancer was observed in women who carried greater numbers of combined high-risk genotypes of BER and NER genes (Ptrend = 0.038). The synergistic effect of multiple genes on risk elevation was significant in women having a longer period of estrogen exposure (>26 years), a longer menarche-to-FFTP interval (>11 years), greater age at the first full-term pregnancy (>26 years), and higher body mass index (>22) (all P<0.05). In conclusion, this study demonstrates that genotype polymorphisms for the DNA damage repair confer higher risk in individual susceptibility to endogenous estrogen on female breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1870.