Esophageal cancer risk by ALDH2 and ADH2 polymorphisms and alcohol consumption: exploration of gene-environment and gene-gene interactions.
Alcohol drinking is a major risk factor for esophageal cancer in Japan and its impact may be modulated by levels of ALDH2, ADH2 and CYP2E1, three representative alcohol-metabolizing enzymes which display genetic polymorphisms altering individual alcohol-oxidizing capacity and drinking behavior. To assess the actual influence of ADH2 Arg47His, ALDH2 Glu487Lys and CYP2E1 variant c2 allele polymorphisms on esophageal cancer risk with conjunction with alcoholic consumption, the present 1:3 matched case-control study was conducted. The 165 histologically diagnosed Japanese esophageal cancer cases were here compared with 495 randomly selected controls, matched with respect to sex and age. Conditional logistic regression was used to calculated Odds Ratios (ORs) and 95% confidence intervals (95% CI). Significant gene-environment interactions between alcohol drinking and both ADH2 and ALDH2 were observed regarding esophageal cancer risk. The ADH2 Arg47His polymorphism showed moderately increased risk (OR for Arg/His and Arg/Arg relative to His/His: 2.01 (1.39-2.90)). In the ALDH2 case, comparing the Glu/Lys with the Glu/Glu genotype, ORs were markedly increased to 9.64 (3.23-28.8) and 95.4 (28.7-317) from 1.88 (0.42-8.37) and 4.62 (0.93-23.1) for moderate drinking and heavy drinking, respectively. No significant alteration in risk was observed with the CYP2E1 polymorphism. In conclusion, the present study revealed a significant gene-environment interaction between alcohol drinking and the ALDH2 polymorphism regarding esophageal cancer risk among a general population in Japan, providing concrete evidence of a role for acetaldehyde in neoplastic development. Interactions between ALDH2 and ADH2 need further clarification.
Yang
Chun-Xia
CX
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Matsuo
Keitaro
K
Ito
Hidemi
H
Hirose
Kaoru
K
Wakai
Kenji
K
Saito
Toshiko
T
Shinoda
Masayuki
M
Hatooka
Shunzo
S
Mizutani
Kazuko
K
Tajima
Kazuo
K
D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects*; D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D004777:Environment; D004938:Esophageal Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D019392:Cytochrome P-450 CYP2E1; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial