Impact of Multiple Alcohol Dehydrogenase Gene Polymorphisms on Risk of Upper Aerodigestive Tract Cancers in a Japanese Population

Abstract

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 ADH1B (rs1229984) and ADH1C (rs698 and rs1693482), and UAT cancer have been observed, despite strong linkage disequilibrium among them. Moreover, UATcancer was significantly associated with rs1573496 in ADH7, and not with rs1984362 in ADH4. However, little evidence is available concerning ADH4 or ADH7 polymorphisms in Asian populations. We conducted a matched case-control study to clarify the role of ADH polymorphisms in a Japanese population. Cases and controls were 585 patients with UAT cancer and 1,170 noncancer outpatients. Genotyping for ADHs and ALDH2 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 ALDH2. Adjusted odds ratios were significant for rs4148887 and rs3805322 in ADH4, rs1229984 in ADH1B, rs698 and rs1693482 in ADH1C, and rs284787, rs1154460, and rs3737482 in ADH7. We also observed that ADH7 rs3737482 and ADH4 rs4148887 had independently and statistically significant effects on UATcancer. The magnitude of effect of these ADH polymorphisms was greater in subjects who were heavy drinkers, heavy smokers, and had esophageal cancer. These findings show that multiple ADH 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)

Clinical features and prognostic factors in patients with head and neck cancer: Results from a multicentric study

“…Polymorphisms in genes encoding for metabolism of alcohol to acetaldehyde [alcohol dehydrogenase gene family (ADH)] and from acetaldehyde to acetate [aldehyde dehydrogenase 2 (ALDH2)], and CYP2E1 polymorphisms, are suspect in HNC and other alcohol-related cancer aetiology [10][11][12][13][14][15][16][17][18][19]. In particular, a significant protective effect of two single nucleotide polymorphisms (SNPs) towards upper aero-digestive tract cancer (UADT) was reported for two alcohol dehydrogenase genes: ADH1B (rs1229984) and ADH7 (rs1573496) [20].…”

Alcohol consumption and corresponding factors: A novel perspective on the risk factors of esophageal cancer

“…This contradiction may be explained by different linkage disequilibrium patterns among various populations (40,48). ADH7 is mainly expressed in the upper gastrointestinal tract (49), and certain studies showed that single nucleotide polymorphisms of ADH7 were associated with esophageal cancer in alcohol drinkers (50)(51)(52).…”

Variation in gastric alcohol dehydrogenase and the risk of alcohol dependence

“…cymetydyny, ranitydyny, famotydyny, oraz inhibicji przez aspirynę, kwas salicylowy, paracetamol, propranolol) czy chorób żołądka (m.in. zanikowe zapalenia żołądka czy przewlekłe zapalenia błony śluzowej żołądka, w tym spowodowane zakażeniem Helicobacter pylori) [17,24]. Wszelkie uszkodzenia śluzówki żołądka obniżają metabolizm alkoholu w tym organie, ponieważ ADH klasy IV występuje głównie w komórkach powierzchniowych i komórkach szyjki gruczołów śluzowych żołądka.…”

“…cimetidine, ranitidine, famotidine, and inhibition by aspirin, salicylic acid, paracetamol, propranolol) or gastric diseases (e.g. atrophic gastritis or chronic gastritis -also caused by Helicobacter pylori infection) [17,24]. Any type of damage to gastric mucosa reduces the metabolism of alcohol in the stomach, as class IV ADH is mainly present in the superficial cells and in gastric mucous neck cells.…”