Cigarette smoking and telomere length: A systematic review of 84 studies and meta-analysis

Background: Cigarette smoking is a risk factor for ageing-related disease, but its association with biological ageing, indicated by telomere length, is unclear. Methods: We systematically reviewed evidence evaluating association between smoking status and telomere length. Searches were performed in MEDLINE (Ovid) and EMBASE (Ovid) databases, combining variation of keywords smoking and telomere. Data was extracted for study characteristics and estimates for association between smoking and telomere length. Quality of studies was assessed with a risk of bias score, and publication bias was assessed with a funnel plot. 12 test was used to observe heterogeneity. Meta -analysis was carried out to compare mean difference in telomere length by smoking status, and a dose-response approach was carried out for pack-years of smoking and telomere length. A sensitivity analysis was carried out to examine sources of heterogeneity. Results: A total of 84 studies were included in the review, and 30 among them were included in our meta analysis. Potential bias was addressed in half of included studies, and there was little evidence of small study bias. Telomere length was shorter among ever smokers compared to never smokers (summary standard mean difference [SMD]: -0.11 (95% CI -0.16 to -0.07)). Similarly, shorter telomere length was found among smokers compared to non-smokers, and among current smokers compared to never or former smokers. Dose response meta -analysis suggested an inverse trend between pack-years of smoking and telomere length. However, heterogeneity among some analyses was observed. Conclusion: Shorter telomeres among ever smokers compared to those who never smoked may imply mechanisms linking tobacco smoke exposure to ageing-related disease.