Association of Vitamin D Receptor Gene Polymorphism with Renal Cell Carcinoma in Japanese.

Abstract

Molecular epidemiologic studies have reported a relationship between 1α,25 dihydroxyvitamin D3 (1,25(OH)₂D₃) and the development and progression of malignant tumors. (1,25(OH)₂D₃) exerts its biological activity by binding the vitamin D receptor (VDR), while recent studies have demonstrated that VDR gene polymorphisms affect serum levels of (1,25(OH)₂D₃). Serum levels of (1,25(OH)₂D₃) are reported to be significantly lower in patients with renal cell carcinoma (RCC) compared to non-cancer control patients. The purpose of this study was to investigate the TaqI VDR polymorphism in Japanese RCC patients and non-cancer controls in order to determine if an association exists between VDR genotype and the risk of developing RCC as well as clinical risk factors. A total of 102 RCC patients and 204 controls were genotyped for a previously described TaqI restriction fragment length polymorphism (RFLP) of the VDR gene. Products were digested into T allele or the t allele according to the absence or presence of a TaqI restriction site. Individuals were classified as TT, Tt or tt. The genotype TT was statistically more frequent among RCC patients (80.4%) compared to controls (61.8%) (OR = 2.54; 95% CI, 1.44-4.46; p = 0.0006). In addition, the occurrence of the genotype TT was significantly higher in patients with rapid-growth-type group (92.1%) compared to slow-growth-type group (73.4%) (OR = 4.22; 95% CI, 1.15-15.53; p = 0.0175). These data demonstrate that VDR genotype plays an important role in determining the risk of developing more aggressive RCC in Japanese.