The Influence of Alcohol Consumption, Smoking, and Physical Activity on Peripheral Blood Leukocyte Telomere Length
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BACKGROUND: Telomeres are repetitive DNA sequences and associated proteins that cap the ends of chromosomes. Functional telomeres protect genetic information and maintain chromosomal stability. Critically short telomeres are associated with an increased risk of cancer. Telomeres shorten at every DNA replication and due to the nature of their molecular structures are also particularly sensitive to oxidative damage. Consequently, oxidative stress accelerates age-dependent telomere shortening. Certain lifestyle factors affect the oxidant/anti-oxidant balance and can promote oxidative stress. The objectives of this thesis were to determine the effect of alcohol, smoking and physical activity on telomere length in a healthy adult population and to explore an interaction with CYP2E1 and alcohol on telomere length. METHODS: A cross-sectional study design was used to recruit 678 healthy volunteers from 2006 to 2008 from Kingston and Ottawa, Ontario, and Halifax, Nova Scotia. This sub-study included 477 individuals with an available DNA sample and complete questionnaire data. Alcohol consumption, smoking and physical activity were assessed by self-administered questionnaire and CYP2E1 was genotyped by the TaqMan® drug metabolism genotyping assay in the larger study. Relative leukocyte telomere length was measured using multiplex quantitative real-time PCR. Multiple linear regression was used to determine the effect of lifestyle on telomere length while controlling for important covariates. Effect modification by CYP2E1 genotype, specifically the CYP2E1*5B polymorphism, in relation to alcohol was investigated by the inclusion of a product term in the model. RESULTS: Alcohol consumption was not associated with telomere length. The interaction with CYP2E1 was not statistically significant; however, the effect of alcohol on telomere length was qualitatively stronger among those with the normal form of CYP2E1. Current smoking and pack-years smoking were inversely related to telomere length. After adjustment for confounders telomere length was not associated with total physical activity; however, higher vigorous physical activity was associated with longer telomeres. CONCLUSIONS: In recent years, research has demonstrated a relationship between shorter telomeres and age-related diseases, including many forms of cancer. This study found that smoking was inversely associated and vigorous physical activity was positively associated with leukocyte telomere length.