Only 5 out of 9 GWAS breast cancer loci were found to be significantly associated with breast cancer in Tunisians: The rs1219648 (G vs. A allele: OR = 1.36, P = 1 × 10(-3)) and rs2981582 (A vs. G allele: OR = 1.55, P = 3 × 10(-6)) of FGFR2 gene; the rs8051542 of the TNRC9 gene (T vs. C allele: OR = 1.40, P = 4 × 10(-4)); the rs889312 of the MAP3K1 gene (C vs. A allele: OR = 1.33, P = 3 × 10(-3)) and the rs13281615 located on 8q24 (G vs. A allele: OR = 1.21, P = 0.03).
Exercise activity and FGFR2 rs2981582 were confirmed to be associated with breast cancer risk, and were found to significantly interact (P for multiplicative and additive interactions = 0.045 and 0.021, respectively).
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 FGFR2 rs2981582.
The association of the fibroblast growth factor receptor 2 gene (<i>FGFR2</i>) polymorphism rs2981582 with breast cancer has been extensively studied, whereas the role of this polymorphism in non-functioning pituitary adenoma (NFPA) has not been elucidated.
Our findings indicate that the GG genotype of rs12443621 is associated with increased breast cancer risk whereas the GA and AA genotypes of rs2981582 are reduced risk in Han Chinese population.
In attempt to investigate whether FGFR2 polymorphisms are associated with a risk of breast cancer in Chinese women of the Han nationality, we genotyped single-nucleotide polymorphisms (SNPs) of seven FGFR2 sites (rs2981582, rs17102287, rs17542768, rs10510097, rs11200012, rs3750817, rs2981578) in 816 women including 388 breast cancer patients and 428 healthy controls via the polymerase chain reaction single-strand conformation polymorphism procedure as well as sequence detection.
The results suggest these polymorphisms, especially rs1966265 and rs2981578, might be candidate pharmacogenomics factors to the response and prognosis prediction for individualized CET-based chemotherapy in breast cancer patients.
A significant association with BC risk was found with SNP rs2981578 (unadjusted per-allele odds ratio = 1.20, 95% confidence interval 1.03-1.41, P(trend) = 0.02), with the odds ratio estimate similar to that reported in European and Asian subjects.
Our results suggest that the A allele and AA genotype of SNP rs2981578 appear to be protective factors associated with breast cancer, while the CT genotype of SNP rs3750817 is a putative risk factor.
This meta-analysis of case-control studies provides strong evidence that FGFR2 (rs2981582, rs2420946 and rs2981578) polymorphisms were significantly associated with the BC risk.
Our results suggest that the increased breast cancer risk associated with SNP rs2981578 is due to increased FGFR2 signaling activity in stromal fibroblasts, possibly also involving paracrine FGF10 signaling.
Polymorphic variants of 2q35-rs13387042, 3p24-rs4973768, 17q23-rs650490 and FGFR2-rs2981578 were analyzed to test for their association with breast cancer susceptibility.
Results from the current meta-analysis indicates that three novel functional polymorphisms (rs11200014, rs2981579, and rs2981578) in the promoter of FGFR2 gene are associated with breast cancer susceptibility and might be a potential biomarkers for breast cancer risk.
We first validated that the SNPs rs12922061, rs2290203, and rs2981578 were associated with overall breast cancer risk in southeast Chinese women, with the per-allele OR of 1.209 (95%CI: 1.064-1.372), 1.176 (95%CI: 1.048-1.320), and 0.852 (95%CI: 0.759-0.956), respectively.
We observed a statistically significant association between 4 SNPs and breast cancer risk and these 4 SNPs were in strong linkage disequilibrium in the Japanese population. rs2420946 was associated with a population-attributable risk of 17.7%.
This meta-analysis of case-control studies provides strong evidence that FGFR2 (rs2981582, rs2420946 and rs2981578) polymorphisms were significantly associated with the BC risk.
To investigate this inconsistency, we performed a meta-analysis of 37 studies involving a total of 288,142 subjects for rs2981582, rs1219648, and rs2420946 polymorphism of the FGFR2 gene to evaluate the effect of FGFR2 on genetic susceptibility for BC.
In the haplotype analysis, the FGFR2 rs2981582 T / rs2420946 T / rs1219648 G haplotype (ht2) was associated with a significantly increased BC risk compared with the rs2981582 C / rs2420946 C / rs1219648 A haplotype in familial BC and in non-familial early-onset BC (OR = 1.32, 95 % CI 1.06-1.65, P = 0.012; OR = 1.46, 95 % CI 1.11-1.91, P = 0.004, respectively).
Significant associations with breast cancer risk were observed for rs2420946, rs2981579, and rs2981582 with OR (95% CI) per risk allele of 1.19 (1.03-1.39), 1.24 (1.07-1.43), and 1.17 (1.01-1.36), respectively.
Three commonly studied FGFR2 polymorphisms including rs1219648 (A > G), rs2420946 (C > T), and rs2981582 (C > T) were selected to explore their association with risk of development of breast cancer by meta-analysis of published case-control studies.
Four SNPs mapped to 10q26.13/FGFR2 were associated with increased breast cancer risk via an additive model with per-allelic risks (95 % CI) of 1.26 (1.12-1.43) at rs1219648, 1.22 (1.07-1.38) at rs2981582, 1.21 (1.07-1.36) at rs2981579, and 1.18 (1.04-1.35) at rs11200014.
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.
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.