Presentation Abstract

Abstract Number: LB-397
Presentation Title: Shortened telomeres in subjects with heavy alcohol consumption
Presentation Time: Wednesday, Apr 21, 2010, 8:00 AM -11:00 AM
Location: Exhibit Hall A-C, Poster Section 39
Author Block: Mirjam Hoxha, Laura Dioni, Pier Alberto Bertazzi, Daniela Sartore, Rossella Snenghi, Santo D. Ferrara, Massimo Montisci, Andrea Baccarelli, Sofia Pavanello. University of Milan and IRCSS Maggiore Hospital, Milan, Italy, University of Padova, Padova, Italy
Abstract Body: Background: Telomere shortening in peripheral blood lymphocytes, a marker of chromosome instability, has been associated with cancer risk. Heavy alcohol consumption has been linked with oxidative stress and inflammation, two mechanisms that accelerate telomere shortening, as well as with the risk of cancer at multiple sites. Whether alcohol drinking determines telomere shortening has never been evaluated.
Objectives: To investigate the effect of alcohol drinking, as well as of single nucleotide polymorphisms in genes involved in alcohol metabolism, on telomere length.
Methods: We measured relative telomere length by multiplex real-time PCR in peripheral blood lymphocyte DNA from 59 alcohol abusers and 197 controls with variable alcohol use. All subjects were non-smoking Caucasian males living in Northeastern Italy. Abusers were identified through an alcohol abuse/dependence evaluation based on a CAGE-AUDIT questionnaire. Current drinking was higher in abusers (0.04-10 drinks/day; 13 subjects [22%] consuming 4 or more drinks/day) than in controls (0-5.4 drinks/day; 7 subjects [4%] consuming 4 or more drinks/day) [p<0.0001]. Eleven (20%) abusers and 15 (8%) controls had serum γ-glutamyltrasferase (GGT) and/or erythrocyte mean corpuscular volume (MCV), taken as conventional biomarkers of alcohol abuse, above the clinical reference values [p=0.014].
Results: Mean lymphocyte telomere length was 0.41 (0.21-0.68) in abusers and 0.79 (0.30-4.56) in controls [p<0.0001]. In the entire study population, simple linear regression analysis showed that lymphocyte telomere length was inversely associated with the number of drinks (p=0.018) and MCV (p=0.004). The proportion of subjects with MCV and/or GGT above the clinical reference values was associated with telomere shortening only among abusers (p=0.024). Carriers of the common variant homozygous genotype (rs1229984) in the alcohol dehydrogenase ADH1B metabolic gene were more likely to be abusers (p=0.008), had a higher number of drinks (p=0.0003), and showed shorter lymphocyte telomere length (p=0.026). The rs698 ADH1C and rs671 aldehyde dehydrogenase ALDH2 polymorphisms were not associated with lymphocyte telomere length. Linear multiple regression analysis on the entire study population showed that both the number of drinks (p=0.004) and ADH1B genotype (p=0.01) were independently associated with lymphocyte telomere length.
Conclusions: Alcohol abusers had severely shortened telomeres compared to non-abusers. The decrease in telomere length was related with alcohol drinking and ADH1B genotype in both abusers and non-abusers. Future studies are warranted to determine the role of telomere shortening in alcohol carcinogenicity.