Vitamin D Receptor Gene Polymorphisms and Breast Cancer Risk in Kazakhstan

Abstract

IntroductionThe steroid hormone 1,25-dihydroxyvitamin D3 is thought to protect against breast cancer. The activity of 1,25-dihydroxyvitamin D3 is mediated via the vitamin D receptor (VDR), and a number of polymorphisms in the VDR gene have been identified. These result in distinct genotypes, some of which may alter susceptibility to breast cancer. Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs1544410 (BsmI) and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR. A reduced risk has been reported for the BsmI BB genotype which may influence VDR mRNA stability.AimWe have investigated whether specific VDR gene polymorphisms are associated with breast cancer risk in Kazakhstan women.Material and MethodsIn a case–control study, female breast cancer patients (315) and a female control group (n=604) were tested for two VDR polymorphisms. Statistical analysis was conducted using SPSS19.0.Results: The VDR rs2228570 (FokI) polymorphism was associated with an increased occurence of BC [rs2228570 (folk) ff vs. FF genotype: OR=1.71; 95% CI=1.21–2.43]. No association was noted between rs1544410 (BsmI) BB and breast cancer risk [OR=0.68; 95% CI=0.49–0.95].Conclusion: Although the factors that increase breast cancer susceptibility remain uncertain, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status. Additional testing on the effect of varying genotypes on the functional mechanisms of the VDR could help to improve future testing and treatment of woman at risk for breast cancer.

Association between Vitamin D receptor (Cdx2, Fok1, Bsm1, Apa1, Bgl1, Taq1, and Poly (A)) gene polymorphism and breast cancer: A systematic review and meta-analysis

“…13,14 To date, only a few VDR gene variants have been considered in relation to BC risk with contradictory results including Fok1, Bsm1, Taq1, Apa1, Cdx2, and Poly (A). 13–47 This inconsistency in results may because of small sample size, low statistical power, and clinical heterogeneity in these studies. 48 In order to resolve the inconsistencies among studies and reduce the likelihood of having false-positive or false-negative relations due to random errors, we executed a meta-analysis of 34 existing studies.…”

Associations of vitamin D receptor encoding gene variants with premenopausal breast cancer risk

“…Other less studied polymorphisms are Cdx2 (rs11568820) (Arai et al, 2001; Iqbal et al, 2015) and EcoRV (rs4516035) (Halsall et al, 2004) the promoter region polymorphisms may affect translation initiation. Previous research aimed at exemplifying the interplay between VDR SNPs and breast cancer risk has documented positive, inverse and null outcomes among different populations (Akilzhanova et al, 2014; Elzehery et al, 2017; Guo et al, 2015; Hashemi et al, 2017; Nemenqani et al, 2015; Reimers et al, 2015; Talaneh et al, 2016). Few studies have been conducted on Asian populations.…”