The known role of FGFR2 signalling, the occurrence of FGFR2 gene amplification in breast cancer and the location of the risk SNPs (single-nucleotide polymorphism) within its intron, make FGFR2 a plausible mediator of risk. Functional studies suggest that the risk allele increases FGFR2 gene expression, most likely in mammary epithelial cells, but recent genotypeexpression correlations in breast tumours have failed to confirm an association of the risk SNPs either with expression of FGFR2 or with other nearby potential target genes. However, studies in the mouse have shown that FGFR2 has an important role in mammary development and in maintenance of breast tumour initiating cells, consistent with a role for FGFR2 in conferring risk.
Fletcher M N C, Castro M A A, Wang X, et al. Master regulators of FGFR2 signalling and breast cancer risk[J]. Nature communications, 2013, 4.