Pooled analysis of alcohol dehydrogenase genotypes and head and neck cancer: a HuGE review.
Possession of the fast metabolizing alleles for alcohol dehydrogenase (ADH), ADH1B*2 and ADH1C*1, and the null allele for aldehyde dehydrogenase (ALDH), ALDH2*2, results in increased acetylaldehyde levels and is hypothesized to increase the risk of head and neck cancer. To examine this association, the authors undertook a Human Genome Epidemiology review on these three genes and a pooled analysis of published studies on ADH1C. The majority of Asians had the fast ADH1B*2 and ADH1C*1 alleles, while the majority of Caucasians had the slow ADH1B*1/1 and ADH1C*1/2 genotypes. The ALDH2*2 null allele was frequently observed among Asians, though it was rarely observed in other populations. In a pooled analysis of data from seven case-control studies with a total of 1,325 cases and 1,760 controls, an increased risk of head and neck cancer was not observed for the ADH1C*1/2 genotype (odds ratio = 1.00, 95% confidence interval: 0.81, 1.23) or the ADH1C*1/1 genotype (odds ratio = 1.14, 95% confidence interval: 0.92, 1.41). Increased relative risks of head and neck cancer were reported for the ADH1B*1/1 and ALDH2*1/2 genotypes in several studies. Recommendations for future studies include larger sample sizes and incorporation of relevant ADH and ALDH genes simultaneously, as well as other genes. These considerations suggest the potential for the organization of a consortium of investigators conducting studies in this field.
Brennan
Paul
P
International Agency for Research on Cancer, Lyon, France. brennan@iarc.fr
Lewis
Sarah
S
Hashibe
Mia
M
Bell
Douglas A
DA
Boffetta
Paolo
P
Bouchardy
Christine
C
Caporaso
Neil
N
Chen
Chu
C
Coutelle
Christiane
C
Diehl
Scott R
SR
Hayes
Richard B
RB
Olshan
Andrew F
AF
Schwartz
Stephen M
SM
Sturgis
Erich M
EM
Wei
Qingyi
Q
Zavras
Athanasios I
AI
Benhamou
Simone
S
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D016022:Case-Control Studies; D005838:Genotype; D014943:Global Health; D006258:Head and Neck Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D015994:Incidence; D016017:Odds Ratio; D012307:Risk Factors
C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial