Alcohol dehydrogenase 3 and risk of esophageal and gastric adenocarcinomas.
OBJECTIVE
Alcohol increases esophageal squamous carcinoma risk but has been less consistently associated with esophageal adenocarcinoma. Alcohol dehydrogenase catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a carcinogen. The alcohol dehydrogenase gene has several polymorphisms which may lead to faster conversion of ethanol to acetaldehyde, which may increase cancer risk.


METHODS
We undertook a study to examine whether a common polymorphism in the alcohol dehydrogenase 3 gene was associated with a higher risk of esophageal adenocarcinoma using data and biological samples collected for the Esophageal and Gastric Cancer Study (n = 114 esophageal and gastric cardia adenocarcinoma, n = 60 non-cardia gastric carcinoma, n = 23 cases of esophageal squamous cell carcinoma and 160 controls).


RESULTS
Individuals homozygous for ADH ( 3 ) (1-1) had a higher risk of each tumor type compared to individuals who had ADH ( 3 ) (2-2) or ADH ( 3 ) (1-2) genotype (OR = 1.7, 95% CI = 1.0-2.9 for esophageal and gastric cardia adenocarcinomas; OR = 1.7, 95% CI = 0.7-4.3 for esophageal squamous cell carcinoma; and OR = 2.8, 95% CI = 1.5-5.1 for non-cardia gastric cancer). The elevation in risk from homozygosity of the ADH ( 3 ) (1) allele was seen in drinkers and nondrinkers, although the risk estimate was only significant for drinkers, particularly of liquor.


CONCLUSIONS
These data suggest ADH3 genotype may be associated with risk of esophageal and gastric cardia adenocarcinomas.
Terry
Mary Beth
MB
Mailman School of Public Health, Department of Epidemiology, Columbia University, 722 West 168th Street, Room 724A, New York, NY 10032, USA. mt146@columbia.edu
Gammon
Marilie D
MD
Zhang
Fang Fang
FF
Vaughan
Thomas L
TL
Chow
Wong-Ho
WH
Risch
Harvey A
HA
Schoenberg
Janet B
JB
Mayne
Susan T
ST
Stanford
Janet L
JL
West
A Brian
AB
Rotterdam
Heidi
H
Blot
William J
WJ
Fraumeni
Joseph F
JF
Santella
Regina M
RM
D000230:Adenocarcinoma / Q000209:etiology*; D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000428:Alcohol Drinking; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D004938:Esophageal Neoplasms / Q000209:etiology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007407:Interviews as Topic; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000209:etiology*; D014481:United States / Q000453:epidemiology
C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase