Interactions between common genetic variants and cigarette smoking before first pregnancy with breast cancer risk in U.S radiologic technologists

Abstract

The role of cigarette smoking in female breast carcinogenesis remains unclear. The increased risk may occurs only from smoking before first pregnancy, when undifferentiated breast tissue may be more susceptible to tobacco carcinogens. In a nested case-control study of 633 breast cancer cases and 835 controls among U.S. radiologic technologists (USRT), we hypothesized the risk from smoking before first pregnancy may be modified by common single nucleotide polymorphisms (SNPs), including 34 SNPs identified through genome-wide association studies (GWAS) and 49 candidate SNPs (13 related to oxidative stress, 17 inflammation, 14 DNA repair, and 5 tobacco metabolism). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression; likelihood ratio tests assessed interaction. Breast cancer risk increased significantly with increasing cumulative pack-years smoked before first pregnancy (OR for every 5 pack-years = 1.10; 95% CI 1.01-1.21) but not after (OR = 0.97, 95% CI 0.92-1.01). Five SNPs significantly (P < 0.05) modified breast cancer risk associated with smoking before first pregnancy, including four GWAS SNPs (CD82-rs7936636, LSP1-rs3817198, STXBP4-rs6504950, 13q33- rs2391406) and one DNA repair SNP (XRCC1-rs25487). However, no interaction remained statistically significant after Bonferroni correction. Our study provides limited evidence that common breast cancer susceptibility loci modify the association between cigarette smoking before first pregnancy and breast cancer risk.