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 stably overexpressed the FN target, MAGE A3, which has also been identified as a target of the breast cancer risk factor fibroblast growth factor receptor 2, and examined the functional effects in vitro and in vivo in a flank model and an orthotopic model of thyroid cancer.
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 breast cancer cell line developed in our laboratory, SUM-52PE, was shown to have a 12-fold amplification of the FGFR2 gene, and FGFR2 message was found to be overexpressed 40-fold in SUM-52PE cells as compared with normal human mammary epithelial (HME) cells.
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.
We found that NEF possessed the anti-growth and anti-metastasis effect on MDA-MB-231 cells through regulating miR-374a/FGFR-2, which might provide new insight for breast cancer management.
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.
Our results demonstrate that the association of SNPs in FGFR2 with BC risk extends to women of African American ethnicity, and illustrate the utility of combining association analysis in datasets of diverse ethnic groups with functional experiments to identify disease susceptibility variants.
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.