We conducted a literature review to identify case-control studies of variants in 4 genes known to affect breast cancer risk: CHEK2*1100delC; multiple variants in BRCA1 and BRCA2; and FGFR2rs2981582.
Significant association with BC was confirmed in 2 SNPs: rs2981582FGFR2 and rs889312 MAP3K1, and the odds ratios of homozygotes with two risk alleles in both SNP's were higher than in heterozygotes with one mutant allele, as follows: FGFR2 TT: 1.953 (95%CI 1.014-3.834, p = 0.049), CT 1.771 (95%CI 1.088-2.899, p = 0.026) and MAP3K1 CC 2.894 (95%CI 1.028-9.566, p = 0.048), AC 1.760 (95%CI 1.108-2.813, p = 0.019).
We evaluated the associations of four genetic variants in the FGFR2 gene highly related to breast cancer risk and the three common tag-SNPs in the FGFR4 gene with skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study (NHS) among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 870 controls.
A dose-dependent association was observed between the risk of breast cancer and the genetic risk score, which was an aggregate measure of alleles in seven selected variants, namely FGFR2-rs2981579, TOX3/TNRC9-rs3803662, C6orf97-rs2046210, 8q24-rs13281615, SLC4A7-rs4973768, LSP1-rs38137198, and CASP8-rs10931936.
Using model systems we show that FGFR2-regulated genes are preferentially linked to breast cancer risk loci in expression quantitative trait loci analysis, supporting the concept that risk genes cluster in pathways.
Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the gene encoding fibroblast growth factor receptor 2 (FGFR2) as a risk factor for breast cancer.
The SNPs of FGFR2rs1219648 and PI3KCA rs6443624 may contribute to the identification of breast cancer patients at risk of more aggressive disease and may be potential prognostic factors in breast cancer in a Chinese population.
This meta-analysis of case-control studies provides strong evidence that fibroblast growth factor 2 (FGFR2; rs11200014, rs2981579, and rs1219648) polymorphisms are significantly associated with the BC risk.
With a lower threshold for preliminary significance to p < 10(-5), we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene.
This meta-analysis demonstrated that FGFR2 polymorphism is a risk factor associated with increased BC susceptibility, but these associations vary in different ethnic populations.
Therefore, the SNPs of TGFB1 rs1982073 and FGFR2rs1219648 may contribute to the identification of patients with more aggressive breast cancers among Han women in North China.
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.
One-third of these loci affected breast cancer oncogenes, whose amplifications were validated with specific probes: 17q12 (two cell lines with ERBB2 amplifications), 11q13 (two with cyclin-D1), 8p11-p12 (two with FGFR1) and 10q25 (one with FGFR2).