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The Associations Between IL-4/IL-4R/IL-13 Immune System Genetic Polymorphism and Risk and Prognosis of Renal Cell Carcinoma

Author: ZuoFu
Tutor: ZhangZhengDong
School: Nanjing Medical University
Course: Occupational and Environmental Health
Keywords: Renal cell carcinoma Interleukin Gene mutation Genetic predisposition Molecular Epidemiology Genetic variation Survival analysis
CLC: R737.11
Type: Master's thesis
Year: 2011
Downloads: 33
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Abstract


The first part IL-4/IL-4R/IL-13 gene polymorphism with renal cell cancer incidence risk research Objective: The incidence and prognosis of renal cell carcinoma has a close relationship with the immune system. IL-4/IL-4R/IL-13 gene as an important part of the immune system, and renal cell cancer occurrence and development process plays an important role. This study is related to the risk of assuming IL-4/IL-4R/IL-13 gene function polymorphic loci with renal cell carcinoma. Methods: A hospital-based case - control study, selection with histologically confirmed 620 new cases of renal cell carcinoma patients as cases, simultaneously choose not suffering from cancer, with the case group does not exist biologically relevant 622 normal subjects as a control . The age and sex of the case group and control group was frequency matching. Multivariate non-conditional logistic regression model analysis of the genetically polymorphic loci with renal cell cancer risk relationship; application stratify analysis methods to analyze the interactions between the gene - environment and gene - gene; application MDR and CART multivariate interaction effects model analysis of the environment - gene, gene - gene interactions. SNPs were selected strategy: biological network database to select a candidate gene located in the promoter region, the gene coding region, 5'-untranslated region, 3'-untranslated region of the base mutation. Minimum allele frequency greater than 0.05, and the Chinese Han population reports. IL-4/IL-4R/IL-13 path in accordance with the above principles, after screening to meet the requirements of the six SNPs are IL-4 gene rs2243250, IL-4R gene rs1801275, rs1805010, rs1805015, IL-13 gene rs20541, rs1800925. TaqMan real time PCR method for genotyping. Results: IL-4R rs1805010 GG genotype as the reference group, AG AA genotype compared the incidence of risk reduced by 34% and 29% (OR = 0.66, 95% CI = 0.51-0.86; OR = 0.71, with a 95% CI = 0.52-0.97). To the rs1805010 locus GG genotype as the reference group, AG / AA joint genotype, compared with a statistically significant (OR = 0.68, 95% CI = 0.53-0.87). The combined effects of genotype analysis showed that the increased risk of suffering from renal cell carcinoma (Ptrend = 0.007) with the carrying of the increase in the number of risk genotypes. The to carry ≤ 5 risk genotypes of individuals as a reference group, carry gt; the risk genotype increases the risk of suffering from renal cell carcinoma (OR = 1.31, 95% CI = 1.04-1.64). Stratify analysis method analysis environment - gene locus, the gene locus - gene locus interaction: the IL-4R gene rs1805010 with diabetes interaction effect (OR = 2.07, 95% CI = 1.29-3.33). Interaction analysis of genetic loci - loci rs1805010 and rs20541 there is an interaction effect (OR = 0.77, 95% CI = 0.61-0.97). The MDR analysis shows: does not exist between the gene - gene interaction effects; gene - environment interaction effects of multifactorial model: high blood pressure, obesity are risk factors for renal cell carcinoma. CART analysis also showed that high blood pressure, obesity is a risk factor for renal cell carcinoma. Conclusion: carrying IL-4R rs1805010 AG / AA genotype can reduce the risk of renal cell carcinoma. The combined effects carry greater than five risk genotypes of individuals suffering from an increased risk of renal cell carcinoma. MDR and CART multi-factor interaction analysis: hypertension plays an important role in the development of renal cell carcinoma. The second part IL-4/IL-4R/IL-13 gene polymorphism and renal cell carcinoma prognosis research purposes: kidney cancer patients with advanced after the five-year survival rate is about 30%, mainly due to single individuals nucleotide polymorphisms caused by genetic differences. This study analyzes the relationship between IL-4/IL-4R/IL-13 gene polymorphism and the risk factors associated with renal cell carcinoma prognosis, in order to obtain a biomarker of prognosis of renal cell carcinoma. Methods: The follow-up selected to meet the requirements of the cases 313 cases, follow-up began in May 2004, the most recent follow-up deadline is October 2010, and every 6 months follow-up time. Log-rank test was used for the survival of the single factor analysis survival curve;; draw the Kaplan-Meier method and Log-rank test to analyze differences in survival time. Multivariate Cox regression model to calculate hazard ratios (hazard ratios, HRs) and 95% confidence intervals (confidence intervals, CIs). All statistical analyzes were performed using SAS software (v9.1; SAS Institute, Cary, NC). The statistical tests were bilateral probability test. Genotyping and gene polymorphic loci selection method described in the first part of. Results: The survival analysis showed that: the average survival time was 18.6 (months). Study demographic characteristics and risk factors: age and hypertension stratified analysis statistically significant P values ??less than 0.05. Gene polymorphic loci with kidney cancer prognosis analysis showed: Log-rank statistical analysis in terms of co-dominant, dominant, recessive model were not found statistically significant risk of polymorphic loci than statistics The analysis found no significant difference between the indicators. Conclusion: Age and hypertension with renal cell carcinoma prognosis is closely related the IL-4/IL-4R/IL-13 gene polymorphism and renal cell cancer prognosis analysis did not find a statistically significant difference. The above findings need large sample studies for validation.

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