Aldehyde Dehydrogenase 2 and Head and Neck Cancer: A Meta-analysis Implementing a Mendelian Randomization Approach
Aldehyde Dehydrogenase 2 and Head and Neck Cancer: A Meta-analysis Implementing a Mendelian Randomization Approach
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DOI：
10.1158/1055-9965.epi-08-0462
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发表时间：
2009-01-01
影响因子：
3.8
通讯作者：
Boffetta, Paolo
中科院分区：
文献类型：
--
作者：
Boccia, Stefania;Hashibe, Mia;Boffetta, Paolo
高剂量饮酒是头颈癌的一个危险因素，而接触酒精的主要代谢物乙醛被认为是增加风险的原因。乙醛脱氢酶2（ALDH 2）*2变异等位基因纯合子的个体不能代谢乙醛，这阻止了他们饮酒，而 *1*2饮酒后的血液乙醛浓度是 *1*1的6倍。根据孟德尔随机化的概念，由于这种多态性在配子形成过程中随机分布，因此其与头颈癌的关联不应受到吸烟的混淆。我们进行了一项关于ALDH 2与头颈癌的荟萃分析，在Medline和Embase上搜索了截至2008年1月31日的相关研究，并通过交互检验调查了从不吸烟者中最大汇总分析中饮酒者的预期比值比（OR）与该荟萃分析中观察到的OR之间的一致性。选择了6项研究（945例病例，2，917例对照）。相对于 *1*1，*2*2中头颈癌的OR为0.53 [95%置信区间（95% CI），0.28-1.00]，*1*2中为1.83（95% CI，1.21-2.77）。*1*1中因饮酒导致头颈癌的预期OR为1.38（95% CI，0.88-2.1.7），该荟萃分析中 *1*1与2*2相比观察到的OR为1.88（95% CI，1.003.57;相互作用P = 0.43）。除了显示孟德尔随机化方法的有效性外，这些发现还支持酒精通过乙醛的致癌作用增加头颈癌风险的理论。（癌症流行病学生物标志物Prev 2009;18（1）：248-54）
Alcohol drinking at high doses is a risk factor for head and neck cancer, and exposure to acetaldehyde, the principle metabolite of alcohol, is supposed to account for the increased risk. Individuals homozygous for the *2 variant allele of aldehyde dehydrogenase 2 (ALDH2) are unable to metabolize acetaldehyde, which prevents them from alcohol drinking, whereas *1*2 have 6-fold higher blood acetaldehyde concentration postalcohol consumption with respect to *1*1. According to the concept of Mendelian randomization, because this polymorphism is distributed randomly during gamete formation, its association with head and neck cancer should be not confounded by smoking. We carried out a meta-analysis of ALDH2 and head and neck cancer searching for relevant studies on Medline and Embase up to January 31, 2008, and investigated the consistency between the expected odds ratio (OR) among drinkers from the largest pooled analysis among never smokers and the observed OR from this meta-analysis by an interaction test. Six studies were selected (945 cases, 2,917 controls). The OR of head and neck cancer among *2*2 was 0.53 [95% confidence interval (95% CI), 0.28-1.00] relative to *1*1 and 1.83 (95% CI, 1.21-2.77) among *1*2. The expected OR for head and neck cancer due to alcohol intake among *1*1 was 1.38 (95% CI, 0.88-2.1.7) and the observed OR among *1*1 compared with 2*2 from this meta-analysis was 1.88 (95% CI, 1.003.57; P for interaction = 0.43). Besides showing the effectiveness of the Mendelian randomization approach, these findings support the theory that alcohol increases head and neck cancer risk through the carcinogenic action of acetaldehyde. (Cancer Epidemiol Biomarkers Prev 2009;18(1):248-54)