Abstract
DNA damage recognition and repair is a complex system of genes focused on maintaining genomic stability. Recently, there has been a focus on how breast cancer susceptibility relates to genetic variation in the DNA bypass polymerases pathway. Race-stratified and subtype-specific logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between 22 single-nucleotide polymorphisms (SNPs) in seven bypass polymerase genes and breast cancer risk in the Carolina Breast Cancer Study, a population-based, case-control study (1,972 cases and 1,776 controls). We used SNP-set kernel association test (SKAT) to evaluate the multi-gene, multi-locus (combined) SNP effects within bypass polymerase genes. We found similar ORs for breast cancer with three POLQ SNPs (rs487848 AG/AA vs. GG; OR = 1.31, 95 % CI 1.03-1.68 for Whites and OR = 1.22, 95 % CI 1.00-1.49 for African Americans), (rs532411 CT/TT vs. CC; OR = 1.31, 95 % CI 1.02-1.66 for Whites and OR = 1.22, 95 % CI 1.00-1.48 for African Americans), and (rs3218634 CG/CC vs. GG; OR = 1.29, 95 % CI 1.02-1.65 for Whites). These three SNPs are in high linkage disequilibrium in both races. Tumor subtype analysis showed the same SNPs to be associated with increased risk of Luminal breast cancer. SKAT analysis showed no significant combined SNP effects. These results suggest that variants in the POLQ gene may be associated with the risk of Luminal breast cancer.