Alcohol, ALDH2, and esophageal cancer: A meta-analysis which illustrates the potentials and limitations of a Mendelian randomization approach
Alcohol, ALDH2, and esophageal cancer: A meta-analysis which illustrates the potentials and limitations of a Mendelian randomization approach
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DOI：
10.1158/1055-9965.epi-05-0196
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发表时间：
2005-08-01
影响因子：
3.8
通讯作者：
Smith, GD
中科院分区：
文献类型：
--
作者：
Lewis, SJ;Smith, GD
孟德尔随机化，在流行病学研究中使用常见的多态性作为测量暴露水平的替代物，提供了一种评估某些环境暴露的因果性质的方法。这可以通过观察ALDH 2多态性与食管癌之间的关联来说明。饮酒被认为是食道癌的一个危险因素，而接触高水平的乙醇（酒精的主要代谢产物）可能是导致癌症风险增加的原因。代谢乙醛的能力由ALDH 2基因编码，该基因在某些人群中具有多态性。ALDH 2 *2等位基因产生一种无活性的蛋白质亚基，其不能代谢乙醛。个体在该位点的基因型可能通过两种机制影响其食管癌风险，第一种是通过影响酒精摄入量，第二种是通过影响乙醛水平。我们对研究ALDH 2基因型和食管癌的研究进行了荟萃分析，发现相对于 *1*1纯合子，*2*2纯合子的风险降低[比值比（OR），0.36; 95%置信区间（95% CI），0.16-0.80]，杂合子的风险增加（OR，3.19; 95% CI，1.86-5.47）。这提供了强有力的证据表明，酒精摄入会增加食管癌的风险，而基因型导致摄入量明显降低的个体，因为他们对酒精有不良反应，因此受到保护。这项荟萃分析还提供了乙醛在食管癌中起致癌作用的证据。作为ALDH 2基因型的结果的两个不同的过程操作具有使用孟德尔随机化范式的研究的解释的影响。
Mendelian randomization, the use of common polymorphisms as surrogates for measuring exposure levels in epidemiologic studies, provides one method of assessing the causal nature of some environmental exposures. This can be illustrated by looking at the association between the ALDH2 polymorphism and esophageal cancer. Alcohol drinking is considered a risk factor for esophageal cancer, and exposure to high levels of acetaldehyde, the principal metabolite of alcohol, may be responsible for the increased cancer risk. The ability to metabolize acetaldehyde is encoded by the ALDH2 gene, which is polymorphic in some populations. The ALDH2*2 allele produces an inactive protein subunit, which is unable to metabolize acetaldehyde. An individual's genotype at this locus may influence their esophageal cancer risk through two mechanisms, first through influencing alcohol intake and second through influencing acetaldehyde levels. We have carried out a meta-analysis of studies looking at the ALDH2 genotype and esophageal cancer and found that risk was reduced among *2*2 homozygotes [odds ratio (OR), 0.36; 95% confidence interval (95% CI), 0.16-0.80] and increased among heterozygotes (OR, 3.19; 95% Cl, 1.86-5.47) relative to *1*1 homozygotes. This provides strong evidence that alcohol intake increases the risk of esophageal cancer and individuals whose genotype results in markedly lower intake, because they have an adverse reaction to alcohol are thus protected. This meta-analysis also provides evidence that acetaldehyde plays a carcinogenic role in esophageal cancer. The two different processes operating as a result of the ALDH2 genotype have implications for the interpretation of studies using the Mendelian randomization paradigm.