title: Shortened telomeres in individuals with abuse in alcohol consumption.
abstract: Alcohol abuse leads to earlier onset of aging-related diseases, including cancer at multiple sites. Shorter telomere length (TL) in peripheral blood leucocytes (PBLs), a marker of biological aging, has been associated with alcohol-related cancer risks. Whether alcohol abusers exhibit accelerated biological aging, as reflected in PBL-TL, has never been examined. To investigated the effect of alcohol abuse on PBL-TL and its interaction with alcohol metabolic genotypes, we examined 200 drunk-driving traffic offenders diagnosed as alcohol abusers as per the Diagnostic and Statistical Manual of Mental Disorders [DSM-IV-TR] and enrolled in a probation program, and 257 social drinkers (controls). We assessed alcohol intake using self-reported drink-units/day and conventional alcohol abuse biomarkers (serum γ-glutamyltrasferase [GGT] and mean corpuscular volume of erythrocytes [MCV]). We used multivariable models to compute TL geometric means (GM) adjusted for age, smoking, BMI, diet, job at elevated risk of accident, genotoxic exposures. TL was nearly halved in alcohol abusers compared with controls (GMs 0.42 vs. 0.87 relative T/S ratio; p<0.0001) and decreased in relation with increasing drink-units/day (p-trend=0.003). Individuals drinking >4 drink-units/day had substantially shorter TL than those drinking ≤4 drink-units/day (GMs 0.48 vs. 0.61 T/S, p=0.002). Carriers of the common ADH1B*1/*1 (rs1229984) genotype were more likely to be abusers (p=0.008), reported higher drink-units/day (p=0.0003), and exhibited shorter TL (p<0.0001). The rs698 ADH1C and rs671 ALDH2 polymorphisms were not associated with TL. The decrease in PBL-TL modulated by the alcohol metabolic genotype ADH1B*1/*1 may represent a novel mechanism potentially related to alcohol carcinogenesis in alcohol abusers.
authors.affiliation: Department of Environmental Medicine and Public Health, Occupational Health Section, Università di Padova, Via Giustiniani 2, 35128 Padova, Italy. sofia.pavanello@unipd.it
authors.forename: Sofia
authors.initials: S
authors.lastname: Pavanello
authors.forename: Mirjam
authors.initials: M
authors.lastname: Hoxha
authors.forename: Laura
authors.initials: L
authors.lastname: Dioni
authors.forename: Pier Alberto
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: Rossella
authors.initials: R
authors.lastname: Snenghi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Nalesso
authors.forename: Santo Davide
authors.initials: SD
authors.lastname: Ferrara
authors.forename: Massimo
authors.initials: M
authors.lastname: Montisci
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
mesh_terms: D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D020751:Alcohol-Induced Disorders / Q000209:etiology*; D000437:Alcoholism / Q000235:genetics*; D016022:Case-Control Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D016615:Telomere / Q000235:genetics*
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase