Evidence for an Important Role of Alcohol- and Aldehyde-Metabolizing Genes in Cancers of the Upper Aerodigestive Tract

摘要: Background: Incidence and mortality rates of upper aerodigestive tract cancers in Central Europe are among the highest world have increased substantially recent years. This increase is likely to be due patterns alcohol tobacco consumption. Genetic susceptibility cancer relation such exposures an important aspect that should investigated populations this region. Methods: A multicenter case-control study comprising 811 cases 1,083 controls was conducted in: Bucharest (Romania), Lodz (Poland), Moscow (Russia), Banska Bystrika (Slovakia), Olomouc Prague (Czech Republic). We analyzed six SNPs three genes related ethanol metabolism: dehydrogenase 1B 1C ( ADH1B, ADH1C ) aldehyde 2 ALDH2 ). Results: The ADH1B histidine allele at codon 48 associated with a decreased risk cancer; odds ratios (OR) were 0.36 [95% confidence interval (95% CI), 0.17-0.77] for medium/heavy drinkers 0.57 CI, 0.36-0.91) never/light drinkers. Moderately risks observed 350Val (OR, 1.19; 95% 0.98-1.55) 272Gln 1.24; 0.98-1.55). Medium/heavy who heterozygous or homozygous nucleotide position 248 significantly 1.76; 1.13-2.75; OR, 5.79; 1.49-22.5, respectively), significant dose response carrying variant alleles P = 0.0007). Similar results +82A>G −261C>T polymorphisms. When by subsite, strong main effects squamous cell carcinoma esophagus all variants. Among 30% population carriers least one variant, attributable fraction (AFc) 24.2% (5.7-38.3%) cancers, increasing 58.7% (41.2-71.0%) esophageal cancer. drank thrice four times week, AFc having 49% (21.3-66.8%) 68.9% (42.9-83.1%) cancer. Conclusions: Polymorphisms European interact (Cancer Epidemiol Biomarkers Prev 2006;15(4):696–703)