Quantitative assessment of the effect of FGFR2 gene polymorphism on the risk of breast cancer

Abstract

Fibroblast growth factor receptor 2 is a tyrosine kinase receptor that is a member of the family of individually distinct fibroblast growth factor receptors involved in cell proliferation, invasiveness, motility, and angiogenesis. Genome-wide association studies have identified FGFR2 as a breast cancer (BC) susceptibility gene in populations of European and Asian descent. After that, a number of studies reported that the rs2981582, rs1219648, and rs2420946 polymorphism in FGFR2 has been implicated in BC risk. However, studies on the association between these polymorphism and BC remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 46,747 cases and 87,342 controls from 16 published case-control studies was performed. Overall, significantly elevated BC risk was associated with rs2981582, rs1219648, and rs2420946 risk allele when all studies were pooled into the meta-analysis. Significant results were also observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. In the subgroup analysis by ethnicity, source of controls, significantly increased risks were found for these polymorphisms in all genetic model. In conclusion, this meta-analysis suggests that rs2981582, rs1219648, and rs2420946 polymorphisms in FGFR2 are associated with elevated BC risk.

Association between FGFR2 (rs2981582, rs2420946 and rs2981578) polymorphism and breast cancer susceptibility: a meta-analysis

“…When stratified by ethnicity and source of controls, the results showed the same association in Asians, Caucasians, hospital populations and general populations, indicating that different genetic backgrounds and living environment were not strong enough to change these associations. All the results for the two variants (rs2981582, rs2420946) were partially consistent with the consequences of Wang's [13], Peng's [14], Zhang's [12] and Jia's [15] meta-analysis, while they didn't conduct analysis in different source of controls, making our results more valuable. Furthermore, they didn't use all the five genetic models(allele model, dominant model, recessive model, homozygous model and heterozygous model) to assess the strength of association.…”

“…These different conclusions may result from the diversity of genetic background and carcinogenic factors, therefore, further studies in different populations should be implemented to assess the correlation between SNPs and BC risk. Although five meta-analysis [11–15] on the associations between FGFR2 (rs2981582, rs2420946 and rs2981578) polymorphism and BC risk had been implemented, yet the results remained inconclusive and some just no subgroup. Therefore, we carried out this meta-analysis on all the included case-control researches to make a more accurate assessment of the relationship.…”

Association of Genome-Wide Association Study (GWAS) Identified SNPs and Risk of Breast Cancer in an Indian Population

“…Our current data support the conclusions of previous GWAS studies1819 that FGFR2 (a tumour suppressor gene) polymorphisms (rs2981582 and rs2981575), first identified as susceptibility loci for BC in Caucasian population2021, are associated with overall BC. The risk allele frequencies of FGFR2 SNPs were similar to those reported in previous GWAS, with the exception of rs2981575, which was much common in our population.…”

Association of rs1219648 in FGFR2 and rs1042522 in TP53 with Premenopausal Breast Cancer in an Iranian Azeri Population

“…Many authors have reported a significant association between rs1219648 and postmenopausal breast cancer (Liang et al, 2008;Raskin et al, 2008;Prentice et al, 2009;Jia et al, 2010). In a genome wide association study, Hunter and his colleagues found a significant association between rs1219648 and postmenopausal breast cancer (p<0.01) too (Hunter et al, 2007).…”