Tian Jianhai1, Lv Jian1, Zhang Long1, Wang Wei1, Zhang Shumao1, Wang Yiming1, Li Xiaojuan2. 1. Department of Urology, Linyi cancer hospital, No.6 Lingyuan East Street, Lanshan District, Shandong Province, Linyi CIty, China. 2. Department of Urology, Linyi cancer hospital, No.6 Lingyuan East Street, Lanshan District, Shandong Province, Linyi CIty, China. lixiaojj226@163.com.
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.
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.
Entities:
Keywords:
Alcohol drinking; Interaction; Renal cell carcinoma; Single nucleotide polymorphisms; Smoking; Vitamin D receptor
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702