Abstract #3943: DNA repair gene single nucleotide polymorphisms and risk of breast cancer (WEB study)

Abstract

Introduction: The genes involved in the base excision repair (BER) and nucleotide excision repair (NER) pathways that repair damaged single-stranded DNA may affect breast cancer risk. Since carcinogens present in cigarettes and acetaldehyde, a metabolite of ethanol, induce the formation of DNA adducts, polymorphisms in DNA repair genes might lead to increased susceptibility to damage induced by cigarette smoking and alcohol use. We evaluated the associations between nine single nucleotide polymorphisms (SNPs) in the NER and BER pathways and risk of breast cancer and examined modification by smoking and alcohol consumption. Methods: Data were collected as part of a case-control study of breast cancer, diet, and environmental exposures, the Western New York Exposures and Breast Cancer (WEB) Study, conducted between 1996 and 2001. Cases included 1170 women age 35 to 79 years with incident, primary histologically confirmed breast cancer, frequency-matched by age and race to 2115 controls. Demographic and breast cancer risk factor data were collected during in-person interviews conducted by trained interviewers. Genotyping for SNPs in three NER pathway genes (ERCC2_G3049A, ERCC2_K751Q, ERCC4_C27935T, XPC_A197G, XPC_A205C, and XPC_C157T) and two BER pathway genes (OGG1_G163C, XRCC1_C8262T, and XRCC1_T8434C) was performed on the 1099 cases and 1945 controls for whom DNA was available by allelic discrimination real-time PCR with TaqMan probes (call rates for the nine SNPs ranged from 90.8% to 98.9%). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results: Among premenopausal women, the XPC_A205C polymorphism was associated with an increased risk of breast cancer (OR=1.69; 95% CI 1.05-2.72) for the CC genotype compared to the AA genotype. Among postmenopausal women, there was evidence that polymorphisms in ERCC2 and XRCC1 were associated with increased risk for heterozygotes and homozygotes of the variant allele, although not all associations reached formal statistical significance. The associations between these SNPs were not modified by lifetime alcohol consumption. When stratified by smoking habits, a significantly increased risk of breast cancer was observed for the XPC_A197G (OR=1.96; 95% CI 1.08-3.57 for the AA genotype compared to the GG genotype), XRCC1_C8262T (OR=1.69; 95% CI 1.00-2.85 for the TT genotype compared to the CC genotype), and XRCC1_T8434C (OR=1.70; 95% CI 1.06-2.70 for the CC genotype compared to the TT genotype) genes among never smokers only. Conclusion: Polymorphisms in DNA repair genes appear to influence the risk of breast cancer, and these associations are modified by smoking habits, but not alcohol consumption. Supported by the following grants: DAMD-17-03-1-0446, DAMD-17-00-1-0417, P50AA09802, RO1CA92040 and R25CA11395102.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3943.