Alcohol and aldehyde dehydrogenase gene polymorphisms and oropharyngolaryngeal, esophageal and stomach cancers in Japanese alcoholics

Abstract

Alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) gene polymorphisms play roles in ethanol metabolism, drinking behavior and esophageal carcinogenesis in Japanese; however, the combined influence of ADH2 and ALDH2 genotypes on other aerodigestive tract cancers have not been investigated. ADH2/ALDH2 genotyping was performed on lymphocyte DNA samples from Japanese alcoholic men (526 cancer-free; 159 with solitary or multiple aerodigestive tract cancers, including 33 oropharyngolaryngeal, 112 esophageal, 38 stomach and 22 multiple primary cancers in two or three organs). After adjustment for age, drinking and smoking habits, and ADH2/ALDH2 genotypes, the presence of either ADH2*1/2*1 or ALDH2*1/2*2 significantly increased the risk for oropharyngolaryngeal cancer [odds ratios (ORs), 6.68 with ADH2*1/2*1 and 18.52 with ALDH2*1/2*2] and esophageal cancer (ORs, 2.64 and 13.50, respectively). For patients with both ADH2*1/2*1 and ALDH2*1/2*2, the risks for oropharyngolaryngeal and esophageal cancers were enhanced in a multiplicative fashion (OR = 121.77 and 40.40, respectively). A positive association with ALDH2*1/2*2 alone was observed for stomach cancer patients who also had oropharyngolaryngeal and/or esophageal cancer (OR = 110.58), but it was not observed for those with stomach cancer alone. Furthermore, in the presence of ALDH2*1/2*2, the risks for multiple intra-esophageal cancers (OR = 3.43) and for esophageal cancer with oropharyngolaryngeal and/or stomach cancer (OR = 3.95) were higher than the risks for solitary intra-esophageal cancer and for esophageal cancer alone, but these tendencies were not observed for ADH2*1/2*1 genotype. Alcoholics' population attributable risks due to ADH2/ALDH2 polymorphisms were estimated to be 82.0% for oropharyngolaryngeal cancer and 63.9% for esophageal cancer.

Influence of alcohol consumption and gene polymorphisms ofADH2andALDH2on hepatocellular carcinoma in a Japanese population

“…Previous case-control studies 20,21 showed consistently positive associations of the ALDH2*1/*2 genotype with the risk for esophageal cancer in East Asian heavy drinkers, and this enzyme-related vulnerability may extend to light to moderate drinkers. Several studies 20,22 also suggest similar associations with the risk of head and neck cancer in Japanese moderate to heavy drinkers.…”

“…Several studies 20,22 also suggest similar associations with the risk of head and neck cancer in Japanese moderate to heavy drinkers. Although some researchers studied the possible associations between these polymorphisms and HCC, [23][24][25][26] the results have been inconsistent.…”

Genotyping of Polymorphisms in Alcohol and Aldehyde Dehydrogenase Genes by Direct Application of PCR-RFLP on Dried Blood without DNA Extraction

“…The PCR products were digested overnight with MaeIII and MboII for ADH1B and ALDH2, respectively. 8,9 Protocols were recently introduced that allow PCR amplification from whole blood or dried blood spotted on filter paper without DNA extraction. [10][11][12][13][14][15] Here, we describe a simplified and rapid PCR-RFLP assay that can be performed on blood dried on paper.…”

Contribution of the alcohol dehydrogenase‐1B genotype and oral microorganisms to high salivary acetaldehyde concentrations in Japanese alcoholic men

“…1 The inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) encoded by ALDH2*1/*2 and the less-active alcohol-dehydrogenase-1B (ADH1B, previously called ADH2) encoded by ADH1B*1/*1 increase the risk of SCC in the UADT in Japanese alcoholic men 2,3 and East Asian drinking populations. [4][5][6] Most homozygotes for inactive ALDH2 are nondrinkers or occasional drinkers, because they experience severe acetaldehydemia and very unpleasant flushing responses, 4 and East Asians with active ALDH2 or ADH1B*1/*1 are at high risk of developing alcoholism.…”