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• W2051210362 abstract "Reduced DNA repair capacity contributes to genomic instability, a hallmark of carcinogenesis. The link between DNA repair capacity and cancer is especially relevant in breast cancer, where women with suboptimal repair capacity have been reported to have up to a five-fold increase in breast cancer risk compared to women with better repair capacity. We investigated promoter methylation levels of DNA repair-related genes and their association with breast cancer risk among participants of the New York site of the Breast Cancer Family Registry, comparing sisters affected with breast cancer to their unaffected sisters. We analyzed DNA extracted from viable mononuclear cells from 218 sisters (N=538 women) using pyrosequencing assays designed to target CpG islands in the promoter regions of BRCA1, MSH2, and MLH1. Breast cancer risk was not significantly associated with the promoter methylation level of BRCA1 (OR=1.09 [0.98-1.20]), MLH1 (OR=1.18 [0.90-1.54]) or MSH2 (OR=0.87 [0.47-1.59]). We assessed the Spearman correlation between methylation and previously generated data on expression level of BRCA1 and MSH2, where we had observed a significant increase in breast cancer risk among women in the lowest quartile of expression for MSH2. Among the affected women, no significant correlation was observed between methylation and expression level for MSH2 (-0.04, p=0.39) or BRCA1 (r=-0.05, p=0.39). These findings suggest that while MSH2 may have implications for breast cancer risk, as suggested by the previously observed increase in risk with decrease in expression level of MSH2, the lack of an association between gene promoter methylation levels of MSH2 and breast cancer risk and the lack of a correlation with expression level in the current study, indicate that other mechanisms impacting the reduction in expression level of this gene may be more relevant to explain the observed increase in breast cancer risk. Citation Format: Maya A. Kappil, Mary Beth Terry, Yuyan Liao, Regina Santella. Variations in promoter methylation levels of DNA repair genes and breast cancer risk in the New York site of the Breast Cancer Family Registry. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 687. doi:10.1158/1538-7445.AM2013-687" @default.
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• W2051210362 date "2013-04-15" @default.
• W2051210362 modified "2023-10-01" @default.
• W2051210362 title "Abstract 687: Variations in promoter methylation levels of DNA repair genes and breast cancer risk in the New York site of the Breast Cancer Family Registry." @default.
• W2051210362 doi "https://doi.org/10.1158/1538-7445.am2013-687" @default.
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