Am J Epidemiol 2004; 159:1-16.
Copyright © 2004 by the Johns
Hopkins Bloomberg School of Public Health
HUMAN GENOME EPIDEMIOLOGY (HuGE) REVIEW |
Pooled Analysis of Alcohol Dehydrogenase Genotypes and Head and Neck Cancer: A HuGE Review
1 International Agency for Research on Cancer, Lyon, France.
2 Environmental Genomics Section, Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC.
3 Geneva Cancer Registry, Institute of Social and Preventive Medicine, University of Geneva, Geneva, Switzerland.
4 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
5 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
6 Department of Medical Biochemistry and Molecular Biology, Bordeaux University, Bordeaux, France.
7 Center for Pharmacogenomics and Complex Disease Research, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark, NJ.
8 Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
9 Department of Head and Neck Surgery and Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, TX.
10 Department of Health Policy and Epidemiology, Harvard School of Dental Medicine, Boston, MA.
11 National Institute of Health and Medical Research and Evry University (EMI 00-06), Evry, France.
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.
ADH1B; ADH1C; alcohol dehydrogenase; aldehyde dehydrogenase; ALDH2; epidemiology; genetics; head and neck neoplasms
Abbreviations: Abbreviations: ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase; ASR, world age-standardized incidence rate per 100,000; CI, confidence interval; CYP, cytochrome P-450; ICD-9, International Classification of Diseases, Ninth Revision; OR, odds ratio.
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