Aldehyde dehydrogenase 2 and head and neck cancer: a meta-analysis implementing a Mendelian randomization approach.
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.
Boccia
Stefania
S
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
Hashibe
Mia
M
Gallì
Paola
P
De Feo
Emma
E
Asakage
Takahiro
T
Hashimoto
Tomoko
T
Hiraki
Akio
A
Katoh
Takahiko
T
Nomura
Takeshi
T
Yokoyama
Akira
A
van Duijn
Cornelia M
CM
Ricciardi
Gualtiero
G
Boffetta
Paolo
P
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
D000431:Ethanol; D000444:Aldehyde Dehydrogenase