Vitamin D receptor gene polymorphisms and its interactions with environmental factors on renal cell carcinoma risk

Abstract

Aims We designed a case-control study to investigate the effect of vitamin D receptor gene (VDR) gene single nucleotide polymorphisms (SNPs) and possible gene- environment interaction on the susceptibility of renal cell carcinoma (RCC). Methods Generalized multifactor dimensionality reduction (GMDR) was used to find out the interaction combinations between SNPs and environmental factors, including gene- gene synergy and gene environment synergy effect. Logistic regression was used to analyze the correlation between the four SNPs in VDR gene and RCC, and the significant interaction combinations found by GMDR model were analyzed by hierarchical analysis. Results The genotype distribution of the control group was in accordance with Hardy- Weinberg equilibrium. Logistic regression analysis showed that the risk of RCC in VDR-rs7975232 A allele carriers was significantly higher than that of CC genotype carriers (CA + AA vs. CC), adjusted OR (95 % CI) = 1.75 (1.26–2.28). We used GMDR model to screen the best synergistic model between the four SNPs of VDR gene and smoking and drinking. We found a significant two locus model (P = 0.0010) involving rs7975232 and smoking. The cross- validation consistency of the two- locus model was 10/ 10, and the accuracy was 60.72 %. Compared with non-smokers with rs7975232 -CA or AA genotype, smokers with rs7975232 -CC genotype had the highest risk of RCC, or (95 % CI) = 2.23 (1.42–3.09), after adjustment for covariates. Conclusions We found that the A allele of rs7975232 within VDR gene, interaction between rs7975232 and smoking were all associated with increased RCC risk.

Association of Interleukin-10 Vitamin D Receptor and Cytochrome P450 1A1 Gene Polymorphisms with Renal Cell Carcinoma Risk

“…There into, 2 studies assessed IL-10-819C/T gene polymorphism and 3 studies [8][9][10] analyzed IL-10-1082A/G gene polymorphism [8,9] . In addition, 7 studies [6,[11][12][13][14][15][16] illustrated the connection between VDR gene polymorphism and the susceptibility to RCC in Table 2. Among these, 5 studies focused on VDR FokI rs2228570 gene polymorphism, 3 studies [6,[11][12][13]16] on VDR ApaI rs7975232, 5 studies [6,[11][12][13][14] on BsmI rs1544410 and 5 studies [6,11,[13][14][15] on VDR TaqI rs731236.…”

“…In addition, 7 studies [6,[11][12][13][14][15][16] illustrated the connection between VDR gene polymorphism and the susceptibility to RCC in Table 2. Among these, 5 studies focused on VDR FokI rs2228570 gene polymorphism, 3 studies [6,[11][12][13]16] on VDR ApaI rs7975232, 5 studies [6,[11][12][13][14] on BsmI rs1544410 and 5 studies [6,11,[13][14][15] on VDR TaqI rs731236. Simultaneously, 5 studies [17][18][19][20][21] retrieved the association between CYP1A1 gene polymorphism with RCC in Table 3.…”