IL-4R 上的 rs4787951 多态性增加了中国人群患肾细胞癌的风险。

Polymorphism rs4787951 in IL-4R contributes to the increased risk of renal cell carcinoma in a Chinese population.

机构信息

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.

出版信息

Gene. 2019 Feb 15;685:242-247. doi: 10.1016/j.gene.2018.11.070. Epub 2018 Nov 23.

DOI:10.1016/j.gene.2018.11.070

PMID:30472377

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.

摘要

目的

白细胞介素是参与肿瘤形成的重要分子。本研究评估了肾细胞癌（RCC）风险与白细胞介素 4/13/4 受体上的单核苷酸多态性（SNP）之间的关联。

方法

我们招募了 620/623 例病例/对照进行病例对照研究。选择了 5 个标签 SNP（即 IL-4R rs8832、IL-4R rs4787951、IL-13 rs1881457、IL-13 rs2066960 和 IL-13 rs2069744）。获得了比值比（OR）及其 95％置信区间（CI），以评估 SNP 与 RCC 易感性之间的关联。进行荧光素酶报告分析和 EMSA 以研究 SNP 是否会影响转录因子与靶基因的结合亲和力。

结果

IL-4R rs4787951T>C 与 RCC 易感性显著相关。与 TT 基因型携带者相比，CC 基因型携带者的 RCC 风险显著增加（调整 OR=1.57，95％CI=1.07-2.28，P=0.020）。通过分层分析，在女性、糖尿病或不吸烟、饮酒和高血压的人群中发现了更明显的关联。此外，SNP rs4787951 可以影响 IL-4R 与转录因子的结合亲和力。等位基因 T 周围的序列易于与转录因子 NFATc 结合。