Polymorphic variants in the vitamin D pathway genes and the risk of ovarian cancer among non-carriers of BRCA1/BRCA2 mutations

Adrianna Mostowska; Stefan Sajdak; Piotr Pawlik; Margarita Lianeri; Paweł P Jagodzinski

doi:10.3892/ol.2015.4033

Polymorphic variants in the vitamin D pathway genes and the risk of ovarian cancer among non-carriers of BRCA1/BRCA2 mutations

Oncol Lett. 2016 Feb;11(2):1181-1188. doi: 10.3892/ol.2015.4033. Epub 2015 Dec 15.

Authors

Adrianna Mostowska¹, Stefan Sajdak², Piotr Pawlik², Margarita Lianeri¹, Paweł P Jagodzinski¹

Affiliations

¹ Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań 60-781, Poland.
² Clinic of Gynecological Surgery, Poznań University of Medical Sciences, Poznań 60-781, Poland.

Abstract

Previous studies have produced inconsistent results regarding the contribution of single-nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) 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 (RXRA), vitamin D-binding protein [also know as group-specific component (GC)] and VDR genes in non-carriers of the breast cancer 1/2 early onset (BRCA1/BRCA2) gene mutations. All participating individuals in the present study were evaluated for BRCA1 mutations (5382incC, C61G and 4153delA) with HybProbe assays, and for BRCA2 mutation (5946delT) using high-resolution melting (HRM) analysis. The associations of 8 SNPs located in RXRA, GC and VDR were investigated in OC patients without the BRCA1/BRCA2 mutations (n=245) and healthy controls (n=465). Genotyping of RXRA rs10881578 and rs10776909, and GC rs1155563 and rs2298849 SNPs was conducted by HRM analysis, while RXRA rs749759, GC rs7041, VDR BsmI rs1544410 and FokI 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 VDR rs1544410 and GC rs2298849 as P_trend=0.012 and P_trend=0.029, respectively. It was also found that, in the dominant inheritance model, VDR BsmI contributed to an increased risk of OC [odds ratio (OR), 1.570; 95% confidence interval (CI), 1.136-2.171; P=0.006; P_corr=0.048]. The gene-gene interaction analysis indicated a significant interaction between RXRA rs749759 and VDR FokI rs2228570 (OR for interaction, 1.687; χ²=8.278; asymptotic P-value=0.004; P_corr=0.032). In conclusion, this study demonstrated that certain VDR and RXRA SNPs may be risk factors for OC in non-carriers of BRCA1/BRCA2 mutations in the Polish population.

Keywords: ovarian cancer; polymorphism; retinoid X receptor; vitamin D receptor; vitamin D-binding protein.