FGFR2 intronic SNPs and breast cancer risk: associations with tumor characteristics and interactions with exogenous exposures and other known breast cancer risk factors.

Recent genome-wide association studies have revealed several new candidate genes for breast cancer, including fibroblast growth factor receptor 2 (FGFR2) gene. The associations were also replicated in several other independent studies. The next important step is to study whether these common variants interact with known breast cancer risk factors, exogenous exposures and tumor characteristics. In a population-based case-control study of 1,170 breast cancer cases and 2,115 controls, we examined genetic associations of four intronic FGFR2 single-nucleotide polymorphisms (SNPs) and breast tumor characteristics and assessed the potential interactions with smoking, alcohol consumption, adiposity and known breast cancer risk factors. FGFR2 variants were significantly associated with breast cancer risk regardless of estrogen and progesterone receptor status, metastasis, lymph node involvement and histologic and nuclear grade. The FGFR2-breast cancer association was modified by smoking status, with increased risk for former and current smokers compared to never smokers; former/current smokers carrying two copies of the rs1219648 minor allele were at highest risk with a crude OR (95% confidence interval) of 2.11 (1.52-2.92) compared to never smokers with no rs1219648 variant alleles. Our study found no evidence for either modification of FGFR2 and breast cancer by alcohol intake or adiposity, even when analyses were stratified by menopausal status. Although these results require further replication, they may provide new insight into the possible new exposures that may interact with FGFR2 susceptibility alleles.