Pooled Analysis of Alcohol Dehydrogenase Genotypes and Head and Neck Cancer: A HuGE Review

Abstract

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.

Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

“…In contrast, the allele rs1229984(G) (ADH1B), which codes for slow metabolizer, is a major allele in Caucasians. 18 The frequency of subjects with two copies of the rs1229984(G) (ADH1B) allele ('slow' metabolizer), of the heterozygous subjects, and of the homozygous carrying two rs1229984(A) (ADH1B) ('fast' metabolizer) was 90%, 9% and o1% in our study, respectively, while it was around 5%, 35% and 60% in studies conducted in Japan. 16,19 This major difference in frequency, that is, degree of genetic exposure, may explain the inconsistency in risk estimates with respect to genetic factors as the statistical power to detect an association will be greater in the Japanese studies than ours.…”

“…10 The allele rs1229984*2 (His) (rs1229984(A) in the present study), which codes for 'fast' metabolism of ethanol, 17 is a frequent allele in Asian populations, while the allele rs1229984*1 (Arg) (rs1229984(G) in the present study) is a major allele in Caucasians. 18 The epidemiological investigations that have so far explored the association between ADH and ALDH polymorphisms and risk of CRC have been of relatively small size and very few data are available from European populations. In light of this, a nested case-control study was conducted within the EPIC, to investigate whether the rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms are associated with CRC risk in European populations, and whether these genes interact with alcohol intake in the aetiology of CRC.…”

Quantitation of an Acetaldehyde Adduct in Human Leukocyte DNA and the Effect of Smoking Cessation

“…Many studies have investigated the relationship between polymorphisms in alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes and cancer, particularly of the head and neck (3,13,14). Polymorphisms in the ADH gene can affect the metabolism of ethanol to acetaldehyde while polymorphisms in the ALDH gene can affect the conversion of acetaldehyde to acetate.…”

A genetic view of laryngeal cancer heterogeneity

“…22 Presenting fast metabolizing alleles for alcohol dehydrogenase (ADH), ADH1B and ALDH2 genes, resulted in increased acetyladehyde levels and associated with HNSCC significantly interacting with alcohol consumption. 23 In a case-control study single nucleotide polymorphisms (SNPs) in nucleotide excision repair (NER) genes such as ERCC5, ERCC6 and RAD23B could modify laryngeal cancer risk. In particular, ERCC6 showed a decreased risk, while ERCC5 and RAD23B increased it.…”