title: Polymorphic variants in the vitamin D pathway genes and the risk of ovarian cancer among non-carriers ofBRCA1/BRCA2mutations.
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)] andVDRgenes in non-carriers of the breast cancer 1/2 early onset (BRCA1/BRCA2) gene mutations. All participating individuals in the present study were evaluated forBRCA1mutations (5382incC, C61G and 4153delA) with HybProbe assays, and forBRCA2mutation (5946delT) using high-resolution melting (HRM) analysis. The associations of 8 SNPs located inRXRA,GCandVDRwere investigated in OC patients without theBRCA1/BRCA2mutations (n=245) and healthy controls (n=465). Genotyping ofRXRArs10881578 and rs10776909, andGCrs1155563 and rs2298849 SNPs was conducted by HRM analysis, whileRXRArs749759,GCrs7041,VDR BsmI rs1544410 andFokI 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 forVDRrs1544410 andGCrs2298849 as Ptrend=0.012 and Ptrend=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; Pcorr=0.048]. The gene-gene interaction analysis indicated a significant interaction betweenRXRArs749759 andVDR FokI rs2228570 (OR for interaction, 1.687; χ2=8.278; asymptotic P-value=0.004; Pcorr=0.032). In conclusion, this study demonstrated that certainVDRandRXRASNPs may be risk factors for OC in non-carriers ofBRCA1/BRCA2mutations in the Polish population.
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań 60-781, Poland.
authors.forename: Adrianna
authors.initials: A
authors.lastname: Mostowska
authors.affiliation: Clinic of Gynecological Surgery, Poznań University of Medical Sciences, Poznań 60-781, Poland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sajdak
authors.affiliation: Clinic of Gynecological Surgery, Poznań University of Medical Sciences, Poznań 60-781, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Pawlik
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań 60-781, Poland.
authors.forename: Margarita
authors.initials: M
authors.lastname: Lianeri
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań 60-781, Poland.
authors.forename: Paweł P
authors.initials: PP
authors.lastname: Jagodzinski
keywords: ovarian cancer; polymorphism; retinoid X receptor; vitamin D receptor; vitamin D-binding protein