新科学想法 › 文献管理 › 浏览文献

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

icecream 添加于 2012-11-3 13:12 | 1088 次阅读 | 0 个评论

作者
Wu C, Kraft P, Zhai K, Chang J, Wang Z, Li Y, Hu Z, He Z, Jia W, Abnet CC, Liang L, Hu N, Miao X, Zhou Y, Liu Z, Zhan Q, Liu Y, Qiao Y, Zhou Y, Jin G, Guo C, Lu C, Yang H, Fu J, Yu D, Freedman ND, Ding T, Tan W, Goldstein AM, Wu T, Shen H, Ke Y, Zeng Y, Chanock SJ, Taylor PR, Lin D
摘要
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 x 10(-39) to P = 2.49 x 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 (P(G x E)) = 4.39 x 10(-11) and P(G x E) = 4.80 x 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 (P(G x E) = 2.54 x 10(-7) to P(G x E) = 3.23 x 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.
详细资料
- 文献种类:期刊
- 期刊名称: Nature Genetics
- 期刊缩写: Nat Genet
- 期卷页: 2012年第44卷第10期 1090-1097页
- 地址: 1] State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. [2] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [3]
- ISBN: 1061-4036
相关链接 DOI URL