Association of vitamin-D receptor (Fok-I) gene polymorphism with bladder cancer in an Indian population


Rama D. Mittal, Sanjay Gandhi PGIMS, Urology and Renal Transplantation, Lucknow, Uttar Pradesh, India. e-mail:



To explore the association of vitamin-D receptor (VDR) genotypes and haplotypes (variants at the Fok-I, and Taq-I sites) with the risk of bladder cancer, as vitamin D is antiproliferative and reported to induce apoptosis in human bladder tumour cells in vitro.


A case-control study using polymerase chain reaction-restriction fragment length polymorphism was conducted in 130 patients with bladder cancer and 346 normal healthy individuals in a north Indian population. Patients were also categorized according to grade and stage of tumour.


There was a significant difference in genotype and allelic distribution of VDR (Fok-I) polymorphism in the patients (P = 0.033 and = 0.017, respectively). The FF genotype was associated with twice the risk for bladder cancer (odds ratio 2.042, 95% confidence interval, CI, 0.803–5.193). There was no significant difference in genotypic distribution or allelic frequencies of the VDR (Taq-I) polymorphism (P = 0.477 and 0.230) when compared with the controls. The stage and grade of the bladder tumours had no association with VDR (Fok-I and Taq-I) genotypes. There was a significant difference in the frequency distribution of the haplotypes FT and fT (P < 0.001); these haplotypes had a protective effect in the control group (odds ratio 0.167, 95% CI 0.096–0.291, and 0.079, 0.038–0.164).


These data suggest that VDR (Fok-I) polymorphism is associated with the risk of bladder cancer. Further, the results for the haplotype FT and fT indicate that patients with this haplotype have a lower risk of developing bladder cancer than those with other haplotypes.