| Partâ… . IL-4/IL-4R/IL-13 genetic polymorphisms association with risk of renal cell carcinoma studyObjective: The pathogenesis of renal cell carcinoma is related to the immune system. IL-4/IL-4R/IL-13 genes as an important component of the immune system,which may play an important role in occurrence and development of renal cell carcinoma. This study hypothesized that the functional polymorphism of IL-4/IL-4R/IL-13 genes association with renal cell cancer risk.Methods: It's a hospital-based case-control study, including the 620 histopathology confirmed new cases of renal cell carcinoma, and 622 controls. The cases and controls were frequency matched in age and sex. Genetic polymorphism association with risk of renal cell carcinoma is analysised by multivariate unconditional logistic regression. Multiple statistical methods were used when estimating the interactive effect of environmental factors and the genetic polymorphisms and gene-gene interaction, including stratified analysis, crossover analysis, multifactor dimensionality reduction (MDR) analysis and classification and regression tree (CART) analysis. SNPs selection strategy, through biological network databases, we selected gene mutation locus located in the promoter region, coding gene region, 5'-untranslated region and 3'-untranslated region of candidate genes. Meanwhile, the minimum allele frequency of genetic polymorphism locus greater than 0.05, and there were reported in Chinese Han population. Accordance with the above principles, after screening in the IL-4/IL-4R/IL-13 pathway to meet the requirements to obtain six SNPs, rs2243250 of IL-4 gene; rs1801275, rs1805010, rs1805015 of IL4R gene; rs20541, rs1800925 of IL-13 gene. Genotyping is used real-time fluorescence PCR method of TaqMan.Results: The gene polymorphism analysis showed that the GG genotype of rs1805010 of IL-4R as reference group, the AG or AA genotype of carrier could decrease risk of renal cell carcinoma when compared with GG genotype of carrier (OR = 0.66, 95% CI = 0.51-0.86; OR =0.71, 95% CI = 0.52-0.97). The GG genotype of rs1805010 as reference group, the AG/AA genotype of carrier have a protective effect (OR = 0.68, 95% CI = 0.53-0.87). It's found that the risk of renal cell carcinoma increasing along with the risk genotype was increasing by combined genotype effects analysis(Ptrend = 0.007). The individuals carried more than five risk genotypes compared with the reference group, the results showed that more than five risk genotypes of individuals suffered from renal cell carcinoma increased (OR = 1.31, 95% CI = 1.04-1.64). The IL-4R rs1805010 and diabetes have interaction effect (OR = 2.07, 95% CI = 1.29-3.33) by stratify analysis method. Gene-gene interaction among in locus analysis showed that rs1805010 and rs20541 have interaction effect (OR = 0.77, 95% CI = 0.61-0.97). There is no interaction between genes by multifactor dimensionality reduction analysis. However it was found that hypertension and obesity were risk factors for renal cell carcinoma in the gene-environment interaction model of MDR. Meanwhile, similar results showed that hypertension and diabetes were risk factors for RCC by CART analysis.Conclusions: The IL-4R rs1805010 AG/AA genotype carrier can reduce the risk of renal cell carcinoma. The combined effect of risk genotype suggested that carried more than 5 risk genotypes of individuals suffering from renal cell cancer risk increased. Hypertension and diabetes were played an important role in the development of renal cell carcinoma by interaction analysis. However, the interaction of gene-gene analysis was not statistically significant. Partâ…¡. IL-4/IL-4R/IL-13 gene polymorphism association with prognosis of renal cell carcinoma studyObjective: The five years of survival rate of advanced patients with kidney cancer surgery was about 30%. Single nucleotide polymorphisms were mainly reason between individuals caused by genetic differences. This study analyzed the polymorphisms of the IL-4/IL-4R/IL-13 genes, risk factors and prognosis of renal cell carcinoma, in order to obtain possible to predict the indicators of renal cell carcinoma.Methods: This follow-up is in line with the requirements of the selected cases are 313, follow-up began with the May 2004, deadline was October 2010, followed up once every six months. The single factor analysis of each relevant factor by Log-rank test, Survival curve is drawn by the Kaplan-Meier method. The different of survival time is tested by the Log-rank test. Multivariate Cox regression model to calculate hazard ratios (hazard ratios, HRs) and 95% confidence interval (confidence intervals, CIs). All analysis is used SAS statistical analysis software package (v9.1; SAS Institute, Cary, NC). Statistical tests are used bilateral probability test. Genotyping and gene polymorphism selection methods are same with part I.Results: The survival analysis showed than average survival time of whole cases were 18.6 (month) The overall demographic characteristics and risk factors analysis showed that age and hypertension have statistically significant in the stratified analyses; P values were less than 0.05. Every gene polymorphism association with prognosis of renal cell carcinoma is analyzed, showing both the co-dominant, dominant, recessive model were not statistically significant by the Log-rank statistical analysis. All the risk of polymorphic loci showed no statistical significance.Conclusion: Age and hypertension association with prognosis of renal cell carcinoma. The gene polymorphism of IL-4/IL-4R/IL-13 pathway association with prognosis of renal cell carcinoma is still not statistically. The results of this study need for a large size of sample ongoing study.
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