Yadi Lin1, Qi Yuan2, Fangze Qian3, Chao Qin4, Qiang Cao4, Meilin Wang2, Haiyan Chu5, Zhengdong Zhang6. 1. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China; Center for Disease Prevention and Control of Gusu District, Suzhou, China. 2. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China. 3. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. 4. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 5. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address: chy_grape@njmu.edu.cn. 6. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address: drzdzhang@njmu.edu.cn.
Abstract
OBJECTIVE: Interleukins are important molecules involved in tumor formation. In this study, the association between renal cell carcinoma (RCC) risk and single nucleotide polymorphisms (SNPs) on IL-4/IL-13/IL-4R was assessed. METHODS: We recruited 620/623 cases/controls and conducted a case-control study. Five tagSNPs (i.e., IL-4R rs8832, IL-4R rs4787951, IL-13 rs1881457, IL-13 rs2066960 and IL-13 rs2069744) were selected. Odds ratios (ORs) with their 95% confidence intervals (CIs) were obtained to appraise the association between SNPs and RCC susceptibility. Luciferase report assay and EMSA were conducted to investigate whether SNPs could affect binding affinity of transcription factors to target genes. RESULTS: IL-4R rs4787951T>C was significantly associated with RCC susceptibility. Individuals carrying CC genotypes had a significant increment in RCC risk compared with TT genotype carriers (adjusted OR = 1.57, 95% CI = 1.07-2.28, P = 0.020). By stratified analyses, more pronounced association was found in the female, diabetic or without smoking, drinking and hypertension group. Besides, SNP rs4787951 could influence the binding affinity of IL-4R to transcription factors. Sequence surrounding allele T was prone to bind transcription factor NFATc. CONCLUSIONS: This study revealed that IL-4R rs4787951T>C was associated with susceptibility of RCC and could be a predictive biomarker for RCC risk.
OBJECTIVE: Interleukins are important molecules involved in tumor formation. In this study, the association between renal cell carcinoma (RCC) risk and single nucleotide polymorphisms (SNPs) on IL-4/IL-13/IL-4R was assessed. METHODS: We recruited 620/623 cases/controls and conducted a case-control study. Five tagSNPs (i.e., IL-4Rrs8832, IL-4Rrs4787951, IL-13rs1881457, IL-13rs2066960 and IL-13rs2069744) were selected. Odds ratios (ORs) with their 95% confidence intervals (CIs) were obtained to appraise the association between SNPs and RCC susceptibility. Luciferase report assay and EMSA were conducted to investigate whether SNPs could affect binding affinity of transcription factors to target genes. RESULTS:IL-4R rs4787951T>C was significantly associated with RCC susceptibility. Individuals carrying CC genotypes had a significant increment in RCC risk compared with TT genotype carriers (adjusted OR = 1.57, 95% CI = 1.07-2.28, P = 0.020). By stratified analyses, more pronounced association was found in the female, diabetic or without smoking, drinking and hypertension group. Besides, SNP rs4787951 could influence the binding affinity of IL-4R to transcription factors. Sequence surrounding allele T was prone to bind transcription factor NFATc. CONCLUSIONS: This study revealed that IL-4R rs4787951T>C was associated with susceptibility of RCC and could be a predictive biomarker for RCC risk.