title: Carcinogenetic impact of ADH1B and ALDH2 genes on squamous cell carcinoma risk of the esophagus with regard to the consumption of alcohol, tobacco and betel quid.
abstract: The consumption of alcohol, tobacco and betel quid has been found to be an important contributor to esophageal squamous cell carcinoma (ESCC) in Taiwan. The genotoxic effect of the ADH1B and ALDH2 genes modulating an individual's alcohol-metabolizing capacity on ESCC may be linked to drinking behavior, intake pattern and other exogenous factors. To investigate the interplay of these genetic and environmental factors in determining the risk of ESCC, a multicenter case-control study was conducted. Here, 406 patients with pathology-proven ESCC, as well as 656 gender, age and study hospital matched controls were recruited. Genetic polymorphisms of ADH1B and ALDH2 appeared to correlate with the abstinence of alcohol, though not with tobacco and betel quid. Within the same levels of alcohol consumption, carcinoma risks increased along with an increase in the numbers of ADH1B*1 and ALDH2*2 alleles. The inactive ALDH2*1/*2 genotype was found to multiplicatively interact with a low-to-moderate (0.1-30 g/day) and a heavy (>30 g/day) ethanol intake to increase the ESCC risk (the joint aOR = 14.5 and 102.6, respectively). Among low-to-moderate drinkers, a smoking-dependent carcinogenetic effect for the ADH1B*1/*1 and ALDH2*1/*2+*2/*2 genotypes was recognized, with significant risks found in smokers, but not in nonsmokers. Further, a supra-multiplicative combined risk of ESCC for alcohol and tobacco use was identified among carriers of the ADH1B*1/*1 genotype (p for interaction = 0.042). In conclusion, the interplay of the ADH1B and ALDH2 genotypes, in conjunction with a behaved drinking habit and a practiced drinking pattern, along with continued tobacco consumption, plays an important pathogenic role in modulating ESCC risk.
authors.affiliation: Faculty of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Lee
authors.forename: Jang-Ming
authors.initials: JM
authors.lastname: Lee
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
authors.forename: Yih-Gang
authors.initials: YG
authors.lastname: Goan
authors.forename: Shah-Hwa
authors.initials: SH
authors.lastname: Chou
authors.forename: I-Chen
authors.initials: IC
authors.lastname: Wu
authors.forename: Ein-Long
authors.initials: EL
authors.lastname: Kao
authors.forename: Te-Fu
authors.initials: TF
authors.lastname: Chan
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Huang
authors.forename: Pei-Shih
authors.initials: PS
authors.lastname: Chen
authors.forename: Chun-Ying
authors.initials: CY
authors.lastname: Lee
authors.forename: Chia-Tsuan
authors.initials: CT
authors.lastname: Huang
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Huang
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Hu
authors.forename: Yu-Hsiu
authors.initials: YH
authors.lastname: Hung
authors.forename: Ming-Tsang
authors.initials: MT
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000009:adverse effects*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000483:Alleles; D001114:Areca; D001483:Base Sequence; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D016022:Case-Control Studies; D017931:DNA Primers; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D005006:Ethnicity; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D002273:Carcinogens; D017931:DNA Primers; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase