Bummer SNP doesn’t mix with beer for gastric cancer risk
Apr04

Bummer SNP doesn’t mix with beer for gastric cancer risk

A study from led by investigators at the Catalan Institute of Oncology (ICO) in Barcelona has revealed that high consumption of beer combined with a single nucleotide polymorphism (SNP) in the alcohol dehydrogenase gene is associated with a nearly nine-fold increased risk of gastric cancer. Thanks to the lovely folks in the American Association for Cancer Research (AACR) press office who recognize science bloggers as press, I was able to sit in on a press conference this morning at the AACR annual meeting in Orlando where several studies were discussed on genetic and environmental factors in cancer risk. Lead author of this particular study, cancer epidemiologist Eric Duell, Ph.D., presented a study of Europeans on alcohol consumption and risk of gastric cancer due to SNPs in the alcohol dehydrogenase gene, ADH1. Recall from biochemistry that ADH1 and other ADH forms catalyze the rate-limiting step in the ethyl alcohol oxidation to acetaldehyde, a known carcinogen. Acetaldehyde, in turn, is oxidized to acetate by aldehyde dehydrogenases (ALDHs). This is an impressive retrospective analysis. The study data was culled the European Prospective Investigation into Cancer and Nutrition (EPIC), a study of 521,000 individuals aged 35 to 50 who completed diet and alcohol use questionnaires at 23 centers across 10 European countries between 1992 and 1998. A subset, or nested-study, called EurGast examined environmental factors and genetic susceptibility to gastric cancer in 364 cases relative to 1272 controls. When examined as a pool only one SNP was associated with a modest, 30% increased risk for gastric cancer.  Combining this SNP with alcohol consumption data revealed that 60 g EtOH/day increased risk by 75%. (Sixty grams of ethanol per day is the amount present in approximately four 12 oz beers at 5% alcohol by volume, four 5 oz glasses of wine at 12% ABV, or four 1oz shots of 100 proof liquor.) However, the subanalysis of that SNP stratified for alcohol consumption and type of alcohol revealed the big surprise. Consumption as beer, but not wine or liquor, combined with this SNP at both alleles was associated with increased gastric cancer risk of 8.72-fold in this high consumption group (just one allele increased risk by only 33%). This SNP in the ADH1 gene, rs1230025, is an intergenic T→A polymorphism, neither in the promoter or the coding region of the gene. The influence of this SNP has only been evaluated in one study where it was shown to be associated with a lower breath alcohol concentration – and presumably higher acetaldehyde concentration, although not explicitly measured – at late timepoints when normal volunteers are given a challenge of 0.75 g/kg of ethanol. But why is...

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