We tested the hypothesis that vitamin D receptor gene polymorphisms are associated with prostate cancer risk using a case-control study of 108 men undergoing radical prostatectomy and 170 male urology clinic controls with no history of cancer.
Fifty-seven non-Hispanic white case patients with prostate cancer and 169 non-Hispanic white control subjects were genotyped for a previously described microsatellite (CAG repeats) in the AR gene and for a newly discovered poly-A microsatellite in the 3'-untranslated region (3'UTR) of the VDR gene.
To understand the molecular basis for this differential sensitivity to 1,25 D3, we compared growth response to 1,25 d3, vitamin D receptor (VDR) content and VDR transcriptional activity in four well-characterized human prostate cancer cell lines: LNCaP, DU145, PC-3 and ALVA-31.
We hypothesize that an unknown gene or genes in linkage with the polymorphisms is (are) responsible for the relationship between risk of prostate cancer and VDR polymorphisms.
Two other human prostate cancer cell lines studied, PC3 and DU145, express lower levels of functional VDR and are relatively insensitive to growth inhibition by 1,25 D. In this report, we investigated potential mechanisms of the variable antiproliferative activity of 1,25 D. In PC3 cells stably expressing VDR [PC3(VDR)] at levels comparable to LNCaP, 1,25 D treatment resulted in only moderate growth inhibition.
Overall, we observed no significant associations of these VDR polymorphisms with prostate cancer risk: relative risk (RR) = 0.86 [95% confidence interval (CI) = 0.57-1.29] for the BB genotype and RR = 0.92 (95% CI = 0.69-1.22) for the Bb genotype, compared with the bb genotype (results were similar for the TaqI polymorphism).
To understand better the relationship between advanced disease and the vitamin D receptor we compared the vitamin D receptor genotype of 41 patients who died of prostate cancer to 41 controls with no clinical evidence of prostate cancer.
Allelic variation at the 3'-end of the vitamin D receptor (VDR) gene has been associated with a 3-5-fold increased risk of developing prostate cancer and with differences in bone mineralization.
The vitamin D3 receptor gene (VDR) contains a TaqI RFLP that is associated with increased VDR mRNA stability, increased serum levels of 1alpha,25-dihydroxyvitamin D3 (1,25-D3), and decreased risk for prostate cancer.
In contrast to previous reports showing an association between vitamin D receptor polymorphism of a TaqI restriction fragment length polymorphism at codon 352 (genotype tt) and prostate cancer in an American population, the frequency of genotype tt is less than one percent in the Japanese population.
Polymorphism of the vitamin D receptor (VDR) gene has recently been shown to be related to bone mineral density, and also associated with hyperparathyroidism and risk of prostatic carcinoma.
In breast cancer, low vitamin D levels in serum are correlated with disease progression and bone metastases, a situation also noted in prostate cancer and suggesting the involvement of the VDR.
To further investigate the putative link between VDR polymorphisms and prostate cancer, we conducted a case-control study of prostate cancer patients from the Piedmont region of North Carolina.
Recently, associations were observed between prostate cancer (CaP) risk and polymorphisms in the vitamin D receptor (VDR) gene and the androgen receptor (AR) gene.
Among 191 newly diagnosed prostate cancer cases and 304 randomly selected population controls in Shanghai, China, we found no significant association between the BsmI or FokI VDR gene polymorphisms and prostate cancer risk.
These data demonstrate that VDR genotype plays an important role in determining the risk of more clinically advanced and pathologically aggressive prostate cancer which is associated with a higher mortality rate in Japanese men.
In this case-control study of Austrian Caucasians, no statistically significant association of the VDR TaqI polymorphism and prostate cancer risk was found.
The purpose of this study was to investigate the TaqI VDR polymorphism in Japanese prostate cancer patients, Japanese BPH patients and Japanese controls in order to determine if an association exists between VDR genotype and the risk of developing prostate cancer and BPH as well as disease severity.
Our results indicate that the contribution of VDR genotypes to prostate cancer susceptibility might depend on the population studied and its geographic localization, and that VDR genotypes are important in the definition of the genetic risk profile of populations of southern Europe.