Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Gut. 2010 Nov;59(11):1457-64. doi: 10.1136/gut.2009.205724. Epub 2010 Sep 9.
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.
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.
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=4.4×10(-40) and OR=4.13, p=8.4×10(-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.
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.
食管鳞状细胞癌（OSCC）被认为是一种难以治愈的癌症。个体层面上，环境和遗传因素的检测对于预防至关重要。
通过同时分析遗传和环境危险因素，确定 OSCC 的高危人群。
对日本的 1071 例 OSCC 病例和 2762 例对照进行了多阶段全基因组关联研究。
评估了 rs1229984（ADH1B）和 rs671（ALDH2）两个相关单核苷酸多态性（SNP）作为遗传和环境危险因素，以及它们的相互作用。rs1229984（ADH1B）和 rs671（ALDH2）的风险等位基因与 OSCC 高度相关（比值比（OR）=4.08，p=4.4×10(-40)和 OR=4.13，p=8.4×10(-76)）。此外，吸烟和饮酒被确定为 OSCC 发病的危险因素。通过整合遗传和环境危险因素，结果表明，rs1229984 和 rs671 风险等位基因与吸烟和饮酒相结合与 OSCC 相关。与环境或遗传危险因素不超过一个的受试者相比，当同时存在环境和遗传危险因素时，OR 达到 146.4（95%CI 50.5 至 424.5）。没有遗传风险时，饮酒与 OSCC 不相关。在有一个或两个遗传危险因素的人群中，饮酒和吸烟的结合增加了 OSCC 的风险。
ADH1B 和 ALDH2 变体分析对于吸烟和饮酒的高危 OSCC 患者的二级预防具有重要价值。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有相互作用，尤其是与饮酒有相互作用。如果在其他人群中得到复制，这些发现可能为 OSCC 的发生提供新的病理生理途径。
