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Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

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Abstract

BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populations.SUBJECTS/METHODS: A nested case-control study (1269 cases matched to 2107controls by sex, age, study centre and date of blood collection) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the impact of rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms on CRC risk. Using the wild-type variant of each polymorphism as reference category, CRC risk estimates were calculated using conditional logistic regression, with adjustment for matching factors.RESULTS: Individuals carrying one copy of the rs1229984(A) (ADH1B) allele (fast metabolizers) showed an average daily alcohol intake of 4.3 g per day lower than subjects with two copies of the rs1229984(G) allele (slow metabolizers) (P-diff

alcohol consumption alcohol intake European Prospective Investigation into Cancer and Nutrition alcohol dependence Alcoholism (MeSH) behavioral and mental disorders toxicity complications colorectal cancer Colorectal Neoplasms (MeSH) digestive system disease neoplastic disease etiology genetics Primates Mammalia Vertebrata Chordata Animalia (Animals Chordates Humans Mammals Primates Vertebrates) - Hominidae [86215] human common middle age aged female male Caucasian Western-European human ADH1B gene [Hominidae] human alcohol dehydrogenase 1B gene polymorphism allele human ADH7 gene [Hominidae] human alcohol dehydrogenase 7 gene polymorphism human ALDH2 gene [Hominidae] human aldehyde dehydrogenase 2 gene polymorphism 03502 Genetics - General 03508 Genetics - Human 03509 Genetics - Population genetics 07004 Behavioral biology - Human behavior 14006 Digestive system - Pathology 15002 Blood - Blood and lymph studies 15004 Blood - Blood cell studies 21002 Psychiatry - Psychopathology psychodynamics and therapy 21004 Psychiatry - Addiction: alcohol drugs smoking 22501 Toxicology - General and methods 24004 Neoplasms - Pathology clinical aspects and systemic effects 24500 Gerontology Biochemistry and Molecular Biophysics Human Medicine Medical Sciences Population Studies blood blood and lymphatics Gastroenterology Molecular Genetics Oncology Population Genetics Psychiatry Toxicology