Genetic polymorphisms in alcohol metabolism, alcohol intake and the risk of stomach cancer in Warsaw, Poland.
Genetic variations increasing blood levels of acetaldehyde, the first metabolite of alcohol, refrain their carriers from drinking alcohol but may also put them at increased risk of cancer because of the mutagenic and carcinogenic effect of acetaldehyde. In a population-based study of 305 cases and 428 controls in Warsaw, Poland, we evaluated the effect of polymorphisms in alcohol metabolizing genes, including ADH1B (Ex9+5C>T, Ex3+23A>G, Ex3+58A>T and Ex9+77A>G), ADH1C (Ex8-56A>G and Ex6-14G>A) and ALDH2 (Ex1+82A>G), on levels of alcohol drinking and susceptibility of stomach cancer. We found that among control subjects frequency of alcohol drinking varied by alcohol metabolizing genotype. In particular, the weekly consumption of individuals carrying the AA, GA and GG genotypes of ALDH2 Ex1+82A>G polymorphism were 3.75, 2.26 and 1.53 drinks, respectively (p=0.04). However, none of the assessed polymorphisms in these 3 genes had a measurable effect on stomach cancer risk. When stratified by ALDH2 Ex1+82A>G polymorphism, alcohol-related increases in stomach cancer risk were restricted to individuals with the AG/GG genotypes, with a more than 2-fold risk among daily drinkers (OR=2.63, 95% CI=1.00-6.88) and 3-fold risk (OR=3.66, 95% CI=1.19-11.24) among those with 40 or more drink-years. In summary, our results suggested that the ALDH2 Ex1+82 G allele may be functionally deficient in eliminating acetaldehyde and discourage alcohol drinking. Furthermore, heavy drinkers of alcohol who were genetically prone to accumulate acetaldehyde may face an increased risk of stomach cancer.
Zhang
Fang Fang
FF
Department of Epidemiology, School of Public Health, University of North Texas Health Science Center, Fort Worth, TX.
Hou
Lifang
L
Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Terry
Mary Beth
MB
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY.
Lissowska
Jolanta
J
Division of Cancer Epidemiology and Prevention, Cancer Center and M. Sklosowska-Curie Institute of Oncology, Warsaw, Poland.
Morabia
Alfredo
A
Center for the Biology of Natural Systems, Queens College-CUNY, Flushing, NY.
Chen
Jinbo
J
Department of Epidemiology and Biostatistics, School of Medicine, University of Pennsylvania, Philadelphia, PA.
Yeager
Meredith
M
Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, Gaithersburg, MD.
Zatonski
Witold
W
Division of Cancer Epidemiology and Prevention, Cancer Center and M. Sklosowska-Curie Institute of Oncology, Warsaw, Poland.
Chanock
Stephen
S
Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, Gaithersburg, MD.
Chow
Wong-Ho
WH
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism*; D000438:Alcohols / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011044:Poland / Q000453:epidemiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism
D000438:Alcohols; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase