Polymorphic variants in the vitamin D pathway genes and the risk of ovarian cancer among non-carriers of mutations.

Previous studies have produced inconsistent results regarding the contribution of single-nucleotide polymorphisms (SNPs) in the vitamin D receptor () gene to ovarian cancer (OC) in various ethnicities. Additionally, little has been established with regard to the role of SNPs located in the retinoid X receptor α (), vitamin D-binding protein [also know as group-specific component ()] and genes in non-carriers of the breast cancer 1/2 early onset () gene mutations. All participating individuals in the present study were evaluated for mutations (5382incC, C61G and 4153delA) with HybProbe assays, and for mutation (5946delT) using high-resolution melting (HRM) analysis. The associations of 8 SNPs located in , and were investigated in OC patients without the mutations (n=245) and healthy controls (n=465). Genotyping of rs10881578 and rs10776909, and rs1155563 and rs2298849 SNPs was conducted by HRM analysis, while rs749759, rs7041, I rs1544410 and I rs2228570 genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. In addition, the gene-gene interactions among all tested SNPs were studied using the epistasis option in PLINK software. The lowest P-values of the trend test were identified for rs1544410 and rs2298849 as P=0.012 and P=0.029, respectively. It was also found that, in the dominant inheritance model, I contributed to an increased risk of OC [odds ratio (OR), 1.570; 95% confidence interval (CI), 1.136-2.171; P=0.006; P=0.048]. The gene-gene interaction analysis indicated a significant interaction between rs749759 and I rs2228570 (OR for interaction, 1.687; χ=8.278; asymptotic P-value=0.004; P=0.032). In conclusion, this study demonstrated that certain and SNPs may be risk factors for OC in non-carriers of mutations in the Polish population.