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.
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.
Lee
Chien-Hung
CH
Faculty of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan.
Lee
Jang-Ming
JM
Wu
Deng-Chyang
DC
Goan
Yih-Gang
YG
Chou
Shah-Hwa
SH
Wu
I-Chen
IC
Kao
Ein-Long
EL
Chan
Te-Fu
TF
Huang
Meng-Chuan
MC
Chen
Pei-Shih
PS
Lee
Chun-Ying
CY
Huang
Chia-Tsuan
CT
Huang
Hsiao-Ling
HL
Hu
Chih-Yang
CY
Hung
Yu-Hsiu
YH
Wu
Ming-Tsang
MT
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*
D002273:Carcinogens; D017931:DNA Primers; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase