Vitamin D receptor gene polymorphisms are associated with increased risk and progression of renal cell carcinoma in a Japanese population.
OBJECTIVE
Biological and epidemiologic data suggest that 1 alpha, 25 dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) levels may influence development of renal cell carcinoma. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of 1,25(OH)(2)D(3) and additionally interacts with other cell signaling pathways that influence cancer progression. VDR gene polymorphisms may play an important role in risk of incidence for various malignant tumors. This study investigated whether VDR gene polymorphisms were associated with increased risk and prognosis of renal cell carcinoma (RCC) in a Japanese population.


METHODS
To analyze risk of RCC depending on VDR polymorphism, a case-control association study was performed. The VDR gene polymorphisms at three locations, BsmI, ApaI and TaqI, were genotyped in 135 RCC patients and 150 controls in a Japanese population. Logistic regression models were used to assess the genetic effects on prognosis.


RESULTS
Significant differences in the ApaI genotype were observed between RCC patients and controls (chi(2) = 6.90, P = 0.032). No statistical significant difference was found in the BsmI and TaqI polymorphisms. The frequency of the AA genotype in the ApaI polymorphism was significantly higher in the RCC patients than in the controls (odds ratio, 2.59; 95% confidence intervals, 1.21-5.55; P = 0.012). Multivariate regression analysis showed that the AA genotype was an independent prognostic factor for cause-specific survival (relative risk 3.3; P = 0.038).


CONCLUSIONS
The AA genotype at the ApaI site of the VDR gene may be a risk of incidence and poor prognosis factor for RCC in the Japanese population. Additional studies with a large sample size and investigation of the functional significance of the ApaI polymorphism in RCC cells are warranted.
Obara
Wataru
W
Department of Urology, Iwate Medical University School of Medicine, Morioka, Japan. watao@iwate-med.ac.jp
Suzuki
Yasushi
Y
Kato
Karen
K
Tanji
Susumu
S
Konda
Ryuichiro
R
Fujioka
Tomoaki
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D016019:Survival Analysis
D018167:Receptors, Calcitriol