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

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) = 1.28 (1.12-1.43), P = 1.7 x 10(-3)), rs2981582[T] (OR = 1.46 (1.30-1.62), P = 2 x 10(-6)) and rs3135718[G] (OR = 1.43 (1.27-1.58), P = 6 x 10(-6)). The latter two SNPs were in strong (r(2) = 0.95) LD in our sample. Maximum likelihood analysis showed that the model, including rs7895676, only explains that the association is significantly (P<0.001) 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. European Journal of Human Genetics (2009) 17, 1688-1691; doi:10.1038/ejhg.2009.98; published online 17 June 2009