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Alcohol drinking at high doses is a risk factor for head and neck cancer, and exposure to acetaldehyde, the principle metabolite of alcohol, is supposed to account for the increased risk. Individuals homozygous for the 2 variant allele of aldehyde dehydrogenase 2 (ALDH2) are unable to metabolize acetaldehyde, which prevents them from alcohol drinking, whereas 1 2 have 6-fold higher blood acetaldehyde concentration postalcohol consumption with respect to 1 1. According to the concept of Mendelian randomization, because this polymorphism is distributed randomly during gamete formation, its association with head and neck cancer should be not confounded by smoking. We carried out a meta-analysis of ALDH2 and head and neck cancer searching for relevant studies on Medline and Embase up to January 31, 2008, and investigated the consistency between the expected odds ratio (OR) among drinkers from the largest pooled analysis among never smokers and the observed OR from this meta-analysis by an interaction test. Six studies were selected (945 cases, 2,917 controls). The OR of head and neck cancer among 2 2 was 0.53 [95% confidence interval (95% CI), 0.28-1.00] relative to 1 1 and 1.83 (95% CI, 1.21-2.77) among 1 2. The expected OR for head and neck cancer due to alcohol intake among 1 1 was 1.38 (95% CI, 0.88-2.17) and the observed OR among 1 1 compared with 2*2 from this meta-analysis was 1.88 (95% CI, 1.00-3.57; P for interaction = 0.43). Besides showing the effectiveness of the Mendelian randomization approach, these findings support the theory that alcohol increases head and neck cancer risk through the carcinogenic action of acetaldehyde.

Original publication

DOI

10.1158/1055-9965.epi-08-0462

Type

Journal article

Journal

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Publication Date

01/2009

Volume

18

Pages

248 - 254

Addresses

Genetic Epidemiology and Molecular Biology Unit, Institute of Hygiene, Università Cattolica del Sacro Cuore, L.go F.Vito 1, 00168 Rome, Italy. sboccia@rm.unicatt.it

Keywords

Humans, Head and Neck Neoplasms, Ethanol, Aldehyde Dehydrogenase, Alcohol Drinking, Causality, Recombination, Genetic, Genotype, Female, Male, Genetic Variation