来自中国医学科学院和中国协和医科大学的林东昕教授及其同事报道了中国人群的食管鳞状上皮细胞癌(ESCC)的全基因组关联研究结果,鉴定到9个新易感位点。他们分析了全基因组的遗传基因与生活环境间的相互作用,证实饮酒是一个已知的促进ESCC发生的风险因素。这些研究结果推进了对ESCC发生机制的认识,同时也为ESCC的预防和治疗提供了潜在的治疗靶标。相关的研究论文于9月9日在线发表在《Nature Genetics》期刊上。

-2012年10月《自然-遗传》

中文翻译


【题目】中国人食管鳞状上皮细胞癌中多个易感位点和基因-环境相互作用

【译文】为阐明食管鳞状细胞癌发生发展的遗传病因,本研究组对2,031例食管鳞状细胞癌患者和2,044例正常个体进行了全基因组关联研究(GWAS),并分析了全基因组基因与环境间的相互作用,进而在独立的8,092例食管鳞状细胞癌患者和8,620例正常个体中进行了验证。本研究组鉴定到9个ESCC易感基因位点,其中7个位点,分别定位在4q23、16q12.1、17q21、22q12、3q27、17p13和18p11染色体区域,具有显著的边际效应(P = 1.78 × 10−39~ 2.49 × 10−11);另外两个位点,定位在2q22和13q33染色体区域,只在基因与饮酒的相互作用中具有显著相关性(遗传基因及生活环境间的交互作用值分别为P (PG × E) = 4.39 × 10−11PG × E = 4.80 × 10−8)。4q23位点内的变异,包括ADH基因簇,每一个与ESCC风险具有相关性的变异均与饮酒有显著的相互作用(PG × E =2.54 × 10−7~PG × E = 3.23 × 10−2)。研究人员还证实了12q24上ALDH2位点与ESCC的相关性,且联合分析显示具有ADH1BALDH2风险等位基因的饮酒者相比于没有这些等位基因的饮酒者,前者患ESCC的风险增加了4倍。新研究阐明了ESCC风险的直接遗传贡献因子,以及通过与饮酒的相互作用促进ESCC发生的遗传因子。

英文原稿


[Title]: Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions 

[Authors]: Chen Wu, Peter Kraft, Kan Zhai, Jiang Chang, Zhaoming Wang, Yun Li, Zhibin Hu, Zhonghu He, Weihua Jia, Christian C Abnet, Liming Liang, Nan Hu, Xiaoping Miao, Yifeng Zhou, Zhihua Liu, Qimin Zhan, Yu Liu, Yan Qiao, Yuling Zhou, Guangfu Jin, Chuanhai Guo, Changdong Lu, Haijun Yang, Jianhua Fu, Dianke Yu, Neal D Freedman, Ti Ding, Wen Tan, Alisa M Goldstein, Tangchun Wu, Hongbing Shen, Yang Ke, Yixin Zeng, Stephen J Chanock, Philip R Taylor & Dongxin Lin

[Abstract]: We conducted a genome-wide association study (GWAS) and a genome-wide gene-environment interaction analysis of esophageal squamous-cell carcinoma (ESCC) in 2,031 affected individuals (cases) and 2,044 controls with independent validation in 8,092 cases and 8,620 controls. We identified nine new ESCC susceptibility loci, of which seven, at chromosomes 4q23, 16q12.1, 17q21, 22q12, 3q27, 17p13 and 18p11, had a significant marginal effect (P = 1.78 × 10−39 to P = 2.49 × 10−11) and two of which, at 2q22 and 13q33, had a significant association only in the gene–alcohol drinking interaction (gene-environment interaction P (PG × E) = 4.39 × 10−11 and PG × E = 4.80 × 10−8, respectively). Variants at the 4q23 locus, which includes the ADH cluster, each had a significant interaction with alcohol drinking in their association with ESCC risk (PG × E = 2.54 × 10−7 to PG × E = 3.23 × 10−2). We confirmed the known association of the ALDH2 locus on 12q24 to ESCC, and a joint analysis showed that drinkers with both of the ADH1B and ALDH2 risk alleles had a fourfold increased risk for ESCC compared to drinkers without these risk alleles. Our results underscore the direct genetic contribution to ESCC risk, as well as the genetic contribution to ESCC through interaction with alcohol consumption.

原文地址

 http://www.nature.com/ng/journal/v44/n10/abs/ng.2411.html

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