Variants of FGFR2 and their associations with breast cancer risk: a HUGE systematic review and meta-analysis

Extensive epidemiological studies have demonstrated that there are associations between variants in intron 2 of FGFR2 and the breast cancer risk in various populations; however, the relationships are not yet conclusively established. To comprehensively review the epidemiological studies showing associations between the variants of FGFR2 and the breast cancer risk, and to establish correlations via a meta-analysis. The PubMed and MEDLINE databases were searched for eligible studies. The associations between the variants and breast cancer risk were evaluated using a random-effects model. The heterogeneity among the studies and the potential publication bias were also evaluated. Fifty-three studies with a total of 121,740 cases and 198,549 controls have examined the associations between 23 variants in intron 2 of FGFR2 and the breast cancer risk. The relationships for the 10 most frequently evaluated variants-rs1078806, rs11200014, rs1219648, rs2420946, rs2981578, rs2981579, rs2981582, rs3135718, rs10736303, and rs3750817-were synthesized based on a meta-analysis. Interestingly, we found that all 10 variants were significantly associated with the risk of breast cancer. In studies stratified by ethnicity, we found that the associations were more notable in Caucasians and Asians compared to Africans. Similar pooled results were found in population-based and hospital-based case-control studies and in studies with small and large sample sizes. FGFR2 is a breast cancer susceptibility gene, and various variants of FGFR2 are significantly associated with the breast cancer risk. However, the biological mechanisms underlying the associations need to be elucidated in future studies.