Association of vitamin D receptor variants with clinical parameters in prostate cancer

Abstract

Purpose Prostate Cancer (PCa) is one of the most common cancers in men and its early detection can provide a high chance of cure. The detection of Vitamin D Receptor (VDR) gene polymorphisms may be useful as a molecular indicator of clinical outcome, once VDR is implicated in a wide variety of biological processes including modulation of the immune response and inhibition of cancer cell growth, angiogenesis and metastasis. In this study we explored the Single Nucleotide Polymorphisms (SNPs) FokI, BsmI, ApaI and TaqI, to evaluate the susceptibility locus for PCa and verify its correlation with clinical parameters.MethodsVDR polymorphisms were detected by PCR followed by Restriction Fragment Length Polymorphism (PCR–RFLP). DNA samples were extracted from peripheral blood of 342 patients: 132 PCa, 41 Benign Prostatic Hyperplasia and 169 young healthy volunteers.Results Statistical analysis showed a noteworthy correlation among SNPs and clinical pathological features. CC genotype (TaqI) was correlated with the age at diagnosis (>58 years old), and GG (BsmI) was associated to lower Prostate-Specific Antigen (PSA) levels (<10 ng/mL). Moreover, when PCa patients were subgrouped, G allele (BsmI) significantly increased the estimated chance for PSA < 10 ng/mL, and GG/GG genotype (BsmI/ApaI) provided a 9.75 fold increased chance of patients with PCa to present lower PSA levels.ConclusionsThe polymorphisms of VDR gene showed a genotype-phenotype association and presented new correlations with different parameters as age and PSA levels.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-2009-8) contains supplementary material, which is available to authorized users.

Vitamin D Receptor Polymorphism and Cancer: An Update

“…However, the results of various studies were disputable and contradictory (39,40). Most of the studies found no association between VDR polymorphism and prostate cancer (13,22), however, Nunes et al found correlation between CC genotype (TaqI) with age (>58 years old), and GG (BsmI) with lower prostate-specific antigen (PSA) levels (<10 ng/ml) (41). Aassociation between a significantly increased estimated chance of PSA <10 ng/ml with G allele (BsmI) and 9.75-fold increased chance of patients with prostate cancer having a lower PSA level with GG/GG genotype (BsmI/ApaI) was also found.…”

“…Aassociation between a significantly increased estimated chance of PSA <10 ng/ml with G allele (BsmI) and 9.75-fold increased chance of patients with prostate cancer having a lower PSA level with GG/GG genotype (BsmI/ApaI) was also found. Recently, various metaanalysis and case-control studies have been conducted to find a relation between VDR polymorphism (TaqI, FokI, Cdx2, ApaI, BsmI, rs731236, rs7975232, rs731236, rs1544410, rs3782905, rs1544410, and rs2239185) and risk of prostate cancer (11,13,18,22,(41)(42)(43)(44). VDR polymorphism FolkI, Cdx2, and ApaI were not found to have any association with an increased risk of prostate cancer.…”

The Association of a Novel Identified VDR SNP With Prostate Cancer in African American Men

“…Both Gleason score and TNM stage are accepted as valid and reliable measures for assessing the aggressiveness of prostate cancer (62). However, Gleason score was found to be a more sensitive measure of aggressive prostate cancer than TNM stage (59,61,63), and the associations of VDR variants with Gleason grade were identified (64). In the present study, we found that carriers of the variant SNP 4 had a significant protective effect and low Gleason score of prostate cancer (β=-0.6, p<0.05); whereas, carriers of SNP 7 had higher risk and poorly differentiated prostate cancer (β=0.…”

Immune Modulation by Vitamin D: Special Emphasis on Its Role in Prevention and Treatment of Cancer

“…59 Gilbert et al 60 have shown that SNPs in VDR correlate with differences in grade and risk, and other studies have shown that VDR FokI polymorphism might be capable of determining susceptibility to PCa. 61,62 VDR expression is involved in the regulation of miRNA-126-3p, miRNA154-5p, and miR-21-5p and of miRNA processing ribonuclease, DICER1, 63 already known to play a role in ovarian Sertoli-Leydig cell tumors. 64 Population studies have shown interesting results; for example, in the Pakistani and Jordanian populations it was possible to identify various VDR polymorphisms that seemed to have a protective effect and others that were associated with a worse prognosis.…”