Association of Genetic Polymorphisms in Vitamin D Receptor Gene and Susceptibility to Sporadic Prostate Cancer

Abstract

Genetic and environmental factors are involved in prostate cancer (PCa) etiology. Single nucleotide polymorphisms (SNPs) may contribute to the PCa pathogenesis. The goal of this study is to determine the role of vitamin D receptor (VDR) gene polymorphisms and haplotypes in the development and progression of sporadic PCa. One hundred and thirty-three PCa patients and 157 age-matched healthy controls were genotyped for the Apa I (rs7975232), Bsm I (rs1544410) and Taq I (rs731236) polymorphisms in VDR gene by using polymerase chain reaction-restriction fragment length polymorphism. An association was observed between the Apa I polymorphism and PCa predisposition (P = 0.03). When compared with AA genotype, there was a highly notable difference in the frequencies of the Aa (P = 0.02), aa (P = 0.026) and Apa I ''a'' allele carriers (Aa + aa) (P = 0.009) genotypes. Furthermore, we found a statistical difference in the allele frequencies of the Apa I polymorphism between the sporadic PCa patients and control subjects (P = 0.013). The genotype distribution for the Bsm I and Taq I polymorphisms were similar between cases and controls (P > 0.05). No clinically significant relationship was found between the three-locus haplotypes and development of sporadic PCa. The genotype frequencies for the three polymorphisms of the VDR gene within subgroups of PCa (defined by tumor stage, Gleason score, PSA levels) were also analyzed, but no statistically noteworthy difference was observed (P > 0.05). As far as we know, this is the first study which investigates the relationship between VDR genotypes and sporadic PCa in the Turkish population. Our findings suggest that the VDR ApaI (rs7975232) polymorphism may play a role in the development of sporadic PCa.

Analysis of Vitamin D Receptor Gene Polymorphisms in Vitiligo

“…The distributions of these polymorphisms were in accordance with the Hardy-Weinberg equilibrium among the controls (p = 0.679, p = 0.294, p = 0.204, p = 0.689 and p = 0.230, respectively). The frequencies of selected polymorphisms were similar to those found in previous studies made in the Turkish population [14,22,23,24] as well as to those in other studies in Caucasian populations [13,25,26]. …”

“…Among these, Bsm I, Apa I, Taq I, Fok I and Cdx2 are the most studied polymorphisms. It has been reported that these polymorphisms are associated with various diseases including psoriasis, diabetes mellitus and cancers [10,11,12,13,14,15,16]. Up to date, there is only one study showing that the Apa I polymorphism of the VDR gene is associated with vitiligo and might play a role in the etiopathogenesis of the disease [17].…”

Vitamin D Gene Pathway Polymorphisms and Risk of Colorectal, Breast, and Prostate Cancer

“…Approximately 30 studies have reported on associations between vitamin D pathway genotypes and risk of prostate cancer (9,13,15,16,21,24,26,27,29,51,53,56,57,62,65,68,70,73,78,83,84,88,89,91,98,99,101,115,128,130) (Supplemental Table 3). A meta-analysis of 14 studies published by Ntais et al (98) in 2003 concluded that four common polymorphisms (BsmI, TaqI, Poly(A) repeat, and FokI) in VDR are unlikely to be major determinants of prostate cancer susceptibility on a population-wide basis.…”

Association between Circulating Vitamin D, the Taq1 Vitamin D Receptor Gene Polymorphism and Colorectal Cancer Risk among Jordanians

“…50.5% and 14%, respectively. Taq1 gene polymorphism genotypes frequencies differ among different ethnicities, different cancer types (Bid et al, 2005), and methodology by which Taq1 VDR polymorphism was investigated, sample size and vitamin D serum levels (Onen et al, 2008). Among Indian individuals the frequencies of Taq1 variants were 49%, 43% and 8% (Bhanushali et al, 2010) while Japanese study showed 77%, 22% and 1% (Minamitani et al, 1998) and a Turkish, study showed frequency of 40.8%, 47.9% and 11.2% (Dilmec et al, 2009) for TT, Tt and tt respectively.…”