Association of FGFR2 gene polymorphisms with the risk of breast cancer in population of West Siberia

Abstract

Polymorphisms within intron 2 of the FGFR2 gene have been associated with increased risk of breast cancer (BC) in European and Asian populations. The study by Easton et al reported two FGFR2 SNPs, rs2981582 and rs7895676, to be among those most strongly associated with BC risk. Statistical modeling suggested that rs7895676 was the variant responsible for the association observed in the region. In this work, we studied the association between seven FGFR2 SNPs, including rs2981582 and rs7895676, and BC risk in the Russian population of 766 case and 665 control women from Siberia, Russian Federation. In our population, allelic frequencies and the magnitude of linkage disequilibrium (LD) were different from those observed in European and Asian populations. The following three SNPs were significantly associated with BC in our study: rs7895676[C] (odds ratio (OR) ¼ 1.28 (1.12 -1.43), P ¼ 1.7 Â 10 À3 ), rs2981582[T] (OR ¼ 1.46 (1.30-1.62), P ¼ 2 Â 10 À6 ) and rs3135718 [G] (OR ¼ 1.43 (1.27-1.58), P ¼ 6 Â 10 À6 ). The latter two SNPs were in strong (r 2 ¼ 0.95) LD in our sample. Maximum likelihood analysis showed that the model, including rs7895676, only explains that the association is significantly (Po0.001) worse than any of the models, including either rs2981582 or rs3135718. Thus, in addition to the confirmation of association of FGFR2 with the BC risk in this new population, our study has suggested that rs7895676 is not likely to represent the causative variant.

Polymorphisms in Second Intron of the FGFR2 Gene Are Associated with the Risk of Early-Onset Breast Cancer in Chinese Han Women

“…In this hospitalbased case-control study, we evaluated the association between 6 SNPs (rs2981428C/A, rs11200014G/A, rs2981579C/T, rs1219648A/G, rs2420946C/T, and rs2981582C/T) of the FGFR2 gene and early-onset breast cancer without a family history by genotyping a southeastern Chinese population of 118 such patients and 104 cancerfree controls. among the six SNPs, the SNP of rs2981428C/A (C23794A) is close to the 3' end of the gene, and may regulate gene expression through the modulation of mRNa stability (Boyarskikh et al 2009). Five of these SNPs (rs11200014G/A, rs2981579C/T, rs1219648A/G, rs2420946C/T, and rs2981582C/T) were associated with breast cancer risk in previous studies (Easton et al 2007;Hunter et al 2007).…”

Current evidence on the relationship between three polymorphisms in the FGFR2 gene and breast cancer risk: a meta-analysis

“…Aberrant expression of alternatively spliced isoforms of FGFR2 transforms breast cancer cells by sustained signal transduction [4][5][6][7][8][9]. In recent years, some original publications [10][11][12][13][14][15][16] have reported the role of FGFR2 polymorphism in breast cancer risk. The association is restricted to single nucleotide polymorphisms (SNPs) in the linkage disequilibrium block covering intron 2, in which three polymorphic variants, rs1219648 (A [ G), rs2420946 (C [ T), and rs2981582 (C [ T), have been the research focus in scientific community and have drawn increasing attention.…”

Genome-wide association of breast cancer: composite likelihood with imputed genotypes

“…Easton et al 1 reported two SNPs, rs2981582 and rs7895676 (at the upstream and downstream boundaries respectively of intron 2), as the most strongly associated and suggested that the latter was most likely to be a causal variant as it showed the strongest association with breast cancer risk. Recently, Boyarskikh et al, 19 studying a West Siberian population, noted that rs2981582 explained association with disease much more strongly than rs7895676. The authors hypothesised that the actual causal variant lies somewhere within the LD block that includes these two SNPs.…”