Associations of polymorphisms in the genes of FGFR2, FGF1, and RBFOX2 with breast cancer risk by estrogen/progesterone receptor status.

Genetic polymorphisms of fibroblast growth factor receptor 2 (FGFR2) have been demonstrated to be associated with breast cancer risk, presumably through elevation of FGFR2 expression. Fibroblast growth factor 1 (FGF1) and RNA binding protein fox-1 homolog 2 (RBFOX2), which are functionally related to FGFR2, may also associate with breast cancer risk. We investigated the associations between breast cancer risk and the polymorphisms of FGFR2 rs2981582, FGF1 rs250108, and RBFOX2 rs2051579 among 839 incident breast cancer cases and 863 age-matched controls in the Guangzhou Breast Cancer Study. Stratified odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by estrogen receptor (ER)/progesterone receptor (PR) status using multivariate logistic regression. FGFR2 rs2981582 was confirmed to be significantly associated with the risk of ER-positive but not ER-negative breast cancer. In contrast, FGF1 rs250108 was significantly associated with the risk of ER-negative breast cancer (OR (95% CI) = 1.68 (1.20-2.35) for CT + TT vs. CC genotype) but not ER-positive breast cancer. CA + AA genotypes at RBFOX2 rs2051579 were associated with a reduced risk of ER-negative (0.71 (0.52-0.97)) but not ER-positive breast cancer compared to the CC genotype. Similar results were observed when differentiating breast cancer cases by PR status. Neither of the pairs between the three SNPs had a significant interaction on breast cancer risk. Our findings show a suggestively stronger association between FGFR2 rs2981582 and ER-positive breast cancer risk and suggest a greater association of FGF1 rs250108 and RBFOX2 rs2051579 with ER-negative compared to ER-positive breast cancer.