Three novel functional polymorphisms in the promoter of FGFR2 gene and breast cancer risk: a HuGE review and meta-analysis

Published data on the association between three novel functional polymorphisms (rs11200014, rs2981579, and rs2981578) in the promoter of FGFR2 gene and breast cancer risk are inconclusive. The aim of this human genome epidemiology review and meta-analysis was to derive a more precise estimation of the relationship. A literature search of Pubmed, Embase, Web of science, and CBM databases from inception through July 2012 was conducted. Seventeen studies were included with a total of 21,742 breast cancer cases and 31,125 healthy controls. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of association in allele model, dominant model, recessive model, homozygous model, and heterozygous model. When all the eligible studies were pooled into the meta-analysis, remarkable associations between the rs11200014 (A>G) polymorphism and breast cancer risk were detected in Caucasians (G vs. A: OR = 1.28, 95 % CI: 1.21–1.35; GG/AG vs. AA: OR = 1.32, 95 % CI: 1.18–1.48), but not in Asians and Africans. In addition, there were statistically significant associations between the rs2981579 (G>A) polymorphism and increased risk of breast cancer risk in all ethnicities (A vs. G: OR = 1.20, 95 % CI: 1.11–1.29; AA/GA vs. GG: OR = 1.32, 95 % CI: 1.18–1.48; AA vs. GG: OR = 1.67, 95 % CI: 1.55–1.81), including Caucasians, Asians, and Africans. However, the TT genotype of rs2981578 (C>T) polymorphism might decrease breast cancer risk (TT vs. CC/CT: OR = 0.55, 95 % CI: 0.38–0.79; TT vs. CC: OR = 0.51, 95 % CI: 0.35–0.76; TT vs. CT: OR = 0.58, 95 % CI: 0.40–0.85), especially among Asians. Results from the current meta-analysis indicates that three novel functional polymorphisms (rs11200014, rs2981579, and rs2981578) in the promoter of FGFR2 gene are associated with breast cancer susceptibility and might be a potential biomarkers for breast cancer risk.