Department of Head and Neck Surgery, Tumor Hospital, Medical College, Shantou University, Shantou, Guangdong Province, China.
Alcohol Clin Exp Res. 2012 Feb;36(2):272-8. doi: 10.1111/j.1530-0277.2011.01621.x. Epub 2011 Sep 6.
Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus, account for approximately 4% of all new cancers in world. Alcohol drinking is an established risk factor for UADT cancers, and the rate of alcohol metabolism could significantly been influenced by genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) His47Arg (rs1229984). To evaluate whether combined evidence shows ADH1B His47Arg as a common genetic variant that influenced the risk of UADT cancers, we considered all available studies in a meta-analysis.
Eighteen studies were combined representing data of 8,539 cases and 15,713 controls for meta-analysis. Stratified analyses were carried out to determine the gene-environment interaction between ADH1B His47Arg and alcohol drinking and gene-gene interaction between ADH1B His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu/Lys related to UADT cancer risk. Potential sources of heterogeneity between studies were explored; sensitivity analysis and publication bias was also evaluated.
The ADH1B 47Arg allele was found to be associated with increased risk of UADT cancers, the pooled odds ratios (ORs) being 1.66 (95% CI: 1.54 to 1.79) and 3.47 (95% CI: 2.76 to 4.36) for the His/Arg and Arg/Arg genotypes compared with the His/His genotype, respectively. An 18.48-fold increase in OR (95% CI: 12.95 to 26.40) for UADT cancers among alcohol drinkers with Arg/Arg genotype was found, when compared among nondrinkers with the His/His genotype. Significant interaction between carriers with ADH1B 47Arg and ALDH2 487Lys allele related to risk for UADT cancers was more evident, compared with noncarriers (OR = 10.31, 95% CI: 5.45 to 18.85).
ADH1B 47Arg allele is a common genetic variant that increased the risk of UADT cancers; furthermore, it modulates the susceptibility to UADT cancers coupled with alcohol drinking and interaction with the ALDH2 487Lys allele.
上呼吸道和消化道癌症（UADT）包括口腔、咽、喉和食管的恶性肿瘤，约占世界所有新发癌症的 4%。饮酒是 UADT 癌症的一个既定危险因素，而酒精代谢率可显著受到乙醇脱氢酶 1B（ADH1B）His47Arg（rs1229984）的遗传多态性影响。为了评估 ADH1B His47Arg 是否作为一个共同的遗传变异，影响 UADT 癌症的风险，我们在荟萃分析中考虑了所有可用的研究。
合并了 18 项研究，代表了 8539 例病例和 15713 例对照的数据分析。进行分层分析以确定 ADH1B His47Arg 与饮酒之间的基因-环境相互作用，以及 ADH1B His47Arg 与与 UADT 癌症风险相关的乙醛脱氢酶 2（ALDH2）Glu/Lys 之间的基因-基因相互作用。探索了研究之间异质性的潜在来源；还评估了敏感性分析和发表偏倚。
ADH1B 47Arg 等位基因与 UADT 癌症风险增加相关，与 His/His 基因型相比，His/Arg 和 Arg/Arg 基因型的合并优势比（ORs）分别为 1.66（95%CI：1.54 至 1.79）和 3.47（95%CI：2.76 至 4.36）。与非饮酒者的 His/His 基因型相比，饮酒者的 Arg/Arg 基因型与 UADT 癌症的 OR 增加了 18.48 倍（95%CI：12.95 至 26.40）。与非携带者相比，携带 ADH1B 47Arg 和 ALDH2 487Lys 等位基因的个体与 UADT 癌症风险的交互作用更为明显（OR=10.31，95%CI：5.45 至 18.85）。
ADH1B 47Arg 等位基因是一个常见的遗传变异，增加了 UADT 癌症的风险；此外，它还调节了与饮酒相关的 UADT 癌症易感性，并与 ALDH2 487Lys 等位基因相互作用。
