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.