Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles
Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles
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DOI：
10.1136/gut.2009.205724
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发表时间：
2010-11-01
期刊：
影响因子：
24.5
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
--
作者：
Tanaka, Fumiaki;Yamamoto, Ken;Mori, Masaki
背景食道鳞状细胞癌(OSCC)被认为是一种难以治愈的癌症。环境和遗传因素的检测对于个体预防具有重要意义。目的通过同时分析遗传和环境危险因素，确定口腔鳞癌的高危人群。方法对1071例日本人和2762名对照的口腔鳞癌进行多阶段全基因组关联研究。结果两个关联的单核苷酸多态(SNPs)以及吸烟和饮酒分别被评估为遗传和环境风险因素，并评估了它们之间的交互作用。风险等位基因rs1229984(ADH1B)和rs671(ALDH2)与口腔鳞癌密切相关(OR分别为4.08，p=4.4×10(-40)和OR=4.13，p=8.4×10(-76))。此外，吸烟和饮酒也被确定为口腔鳞癌的危险因素。综合遗传和环境危险因素，rs1229984和rs671危险等位基因与吸烟和饮酒相结合与口腔鳞癌相关。当环境和遗传危险因素同时存在时，与仅有一个以上环境或遗传危险因素的人群相比，OR值为146.4(95%CI50.5~424.5)。如果没有遗传风险，饮酒与口腔鳞癌没有相关性。在有一个或两个遗传危险因素的人群中，饮酒和吸烟共同增加了口腔鳞癌的风险。结论ADH1B和ALDH2基因变异分析对吸烟和饮酒的高危患者口腔鳞癌的二级预防具有重要意义。在这项研究中，SNP基因分型表明ADH1B和/或ALDH2风险等位基因与吸烟，特别是饮酒存在交互作用。这些发现，如果在其他组中复制，可能为口腔鳞癌的发展展示新的病理生理学途径。
Background Oesophageal squamous cell carcinoma (OSCC) is considered a difficult cancer to cure. The detection of environmental and genetic factors is important for prevention on an individual basis.Objective To identify groups at high risk for OSCC by simultaneously analysing both genetic and environmental risk factors.Methods A multistage genome-wide association study of OSCC in Japanese individuals with a total of 1071 cases and 2762 controls was performed.Results Two associated single-nucleotide polymorphisms (SNPs), as well as smoking and alcohol consumption, were evaluated as genetic and environmental risk factors, respectively, and their interactions were also evaluated. Risk alleles of rs1229984 (ADH1B) and rs671 (ALDH2) were highly associated with OSCC (odds ratio (OR)=4.08, p=4.4 x 10(-40) and OR=4.13, p=8.4 x 10(-76), respectively). Also, smoking and alcohol consumption were identified as risk factors for OSCC development. By integrating both genetic and environmental risk factors, it was shown that the combination of rs1229984 and rs671 risk alleles with smoking and alcohol consumption was associated with OSCC. Compared with subjects with no more than one environmental or genetic risk factor, the OR reached 146.4 (95% CI 50.5 to 424.5) when both environmental and genetic risk factors were present. Without the genetic risks, alcohol consumption did not correlate with OSCC. In people with one or two genetic risk factors, the combination of alcohol consumption and smoking increased OSCC risk.Conclusions Analysis of ADH1B and ALDH2 variants is valuable for secondary prevention of OSCC in high-risk patients who smoke and drink alcohol. In this study, SNP genotyping demonstrated that the ADH1B and/or ALDH2 risk alleles had an interaction with smoking and, especially, alcohol consumption. These findings, if replicated in other groups, could demonstrate new pathophysiological pathways for the development of OSCC.