title: Genetic polymorphisms in alcohol metabolism, alcohol intake and the risk of stomach cancer in Warsaw, Poland.
abstract: 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.
authors.affiliation: Department of Epidemiology, School of Public Health, University of North Texas Health Science Center, Fort Worth, TX.
authors.forename: Fang Fang
authors.initials: FF
authors.lastname: Zhang
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.affiliation: Division of Cancer Epidemiology and Prevention, Cancer Center and M. Sklosowska-Curie Institute of Oncology, Warsaw, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.affiliation: Center for the Biology of Natural Systems, Queens College-CUNY, Flushing, NY.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Morabia
authors.affiliation: Department of Epidemiology and Biostatistics, School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Chen
authors.affiliation: Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, Gaithersburg, MD.
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.affiliation: Division of Cancer Epidemiology and Prevention, Cancer Center and M. Sklosowska-Curie Institute of Oncology, Warsaw, Poland.
authors.forename: Witold
authors.initials: W
authors.lastname: Zatonski
authors.affiliation: Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, Gaithersburg, MD.
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
mesh_terms: 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
chemical_list: D000438:Alcohols; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase