title: Aldehyde dehydrogenase 2 and head and neck cancer: a meta-analysis implementing a Mendelian randomization approach.
abstract: 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.
authors.affiliation: 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
authors.forename: Stefania
authors.initials: S
authors.lastname: Boccia
authors.forename: Mia
authors.initials: M
authors.lastname: Hashibe
authors.forename: Paola
authors.initials: P
authors.lastname: Gallì
authors.forename: Emma
authors.initials: E
authors.lastname: De Feo
authors.forename: Takahiro
authors.initials: T
authors.lastname: Asakage
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Akio
authors.initials: A
authors.lastname: Hiraki
authors.forename: Takahiko
authors.initials: T
authors.lastname: Katoh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nomura
authors.forename: Akira
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Gualtiero
authors.initials: G
authors.lastname: Ricciardi
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D015984:Causality; D000431:Ethanol / Q000009:adverse effects / Q000378:metabolism*; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D011995:Recombination, Genetic / Q000235:genetics
chemical_list: D000431:Ethanol; D000444:Aldehyde Dehydrogenase