Abstract
<div>Abstract<p>Alcohol intake is positively associated with the risk of upper aerodigestive tract (UAT) cancer. The genes that encode alcohol-metabolizing enzymes, primarily alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH), are polymorphic. In Caucasians, significant associations between polymorphisms in <i>ADH1B</i> (rs1229984) and <i>ADH1C</i> (rs698 and rs1693482), and UAT cancer have been observed, despite strong linkage disequilibrium among them. Moreover, UAT cancer was significantly associated with rs1573496 in <i>ADH7</i>, and not with rs1984362 in <i>ADH4</i>. However, little evidence is available concerning <i>ADH4</i> or <i>ADH7</i> polymorphisms in Asian populations. We conducted a matched case-control study to clarify the role of <i>ADH</i> polymorphisms in a Japanese population. Cases and controls were 585 patients with UAT cancer and 1,170 noncancer outpatients. Genotyping for <i>ADHs</i> and <i>ALDH2</i> was done using TaqMan assays. Associations between polymorphisms and UAT cancer were assessed by odds ratios and 95% confidence intervals using conditional logistic regression models that adjusted for age, sex, smoking, drinking, and <i>ALDH2</i>. Adjusted odds ratios were significant for rs4148887 and rs3805322 in <i>ADH4</i>, rs1229984 in <i>ADH1B</i>, rs698 and rs1693482 in <i>ADH1C</i>, and rs284787, rs1154460, and rs3737482 in <i>ADH7</i>. We also observed that <i>ADH7</i> rs3737482 and <i>ADH4</i> rs4148887 had independently and statistically significant effects on UAT cancer. The magnitude of effect of these <i>ADH</i> polymorphisms was greater in subjects who were heavy drinkers, heavy smokers, and had esophageal cancer. These findings show that multiple <i>ADH</i> gene polymorphisms were associated with UAT cancer in this Japanese population. Further studies in various ethnicities are required. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3097–102)</p></div>
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