A comprehensive Review of previous case–control studies investigating the link between alcohol consumption, genetic polymorphisms*, and cancer risk suggests that gene polymorphisms in enzymes—alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)—involved in metabolising alcohol, significantly increase the likelihood that alcohol drinkers will develop upper aerodigestive tract cancers. The Review, published in the February issue of The Lancet Oncology, concludes there are currently insufficient data to determine the effect of polymorphisms in other genes coding for enzymes involved in the metabolism of alcohol or folate.
The link between alcohol consumption and health risk is undisputed. Recent global figures show that drinking alcohol was a major contributory factor in the development of 389 100 cancers in 2002. During that year, 232 900 cancer deaths—representing 3.6 % of all cancer deaths—were alcohol-related.
Metabolism of the alcohol molecule is important in carcinogenesis and genetic susceptibility and the level of alcohol exposure is likely to determine cancer risk. Polymorphisms in any of the genes involved in the conversion of ethanol to acetaldehyde and the oxidation of acetaldehyde to acetate could lead to a spectrum of susceptibility to the carcinogenic effect of moderate and excessive drinking. However, which polymorphisms are definitely linked with cancer is less well known and quantitative data are scarce.
Dr Nathalie Druesne-Pecollo and colleagues therefore used Medline to identify studies on alcohol consumption, genetic polymorphisms, and cancer. They noted that most studies looked at the effect of variation in genes coding for enzymes involved in alcohol and folate metabolism, primarily ADH, ALDH, cytochrome P450 2E1, and methylene-tetrahydrofolate reductase (MTHFR).
Many studies had serious limitations in experimental design, including low statistical power, a failure to take account of important confounding factors and the tendency to focus on only one polymorphism. Nevertheless, there was definite evidence that polymorphisms ADH1B and ALDH2 were associated with an increased risk of cancers of the head and neck and oesophagus in alcohol drinkers. Insufficient data prevented an assessment of the effect of ADH1C, CYP2E1, and MTHFR gene variants on cancer risk.
The authors point out currently available data does not allow quantitative evaluation by meta-analysis of the risk of cancer associated with gene polymorphisms in consumers of alcohol. "We have highlighted the need for large multicentre studies and for approaches to the study of multiple polymorphisms", says Dr Druesne-Pecollo.
Dr Nathalie Druesne-Pecollo, French National Institute of Agronomical Research (INRA), Jouy-en-Josas cedex, France T) + 33 1 34 65 22 60 E) nathalie.pecollo@jouy.inra.fr
For full Review see: http://press.thelancet.com/TLOalcohol.pdf
Notes for editors:
Genetic Polymorphisms: Variations in the DNA of genes
Medline was used to identify relevant studies using specific search terms. There was no date restriction.
Search strategies were limited to cancers of the upper aerodigestive tract, liver, breast and colon-rectum since substantial evidence exists for a positive correlation between these cancers and alcohol consumption.
The authors reviewed only articles in English that described observations in humans.
Journal
The Lancet Oncology