Abstract

ObjectivesTo investigate the link between smoking exposure, telomere length and mortality, with emphasis on second-hand smoke (SHS) exposure and the duration of smoking cessation.ResultsA total of 1,018 participants died during follow-up (mean: 10.3 years). A 50 base-pair decrease in LTL was shown among cotinine-confirmed current versus never smokers. The 90th quantile of LTL decreased with increasing cotinine among never smokers, indicating a role of SHS. Longer telomeres with smoking cessation were indicated but limited to a 3-16 year period of abstaining smoking. When assessing mortality, we observed a lower risk of all-cause death for the second quintile compared to the first among never smokers (HR: 0.67, 95% CI: 0.52-0.87), and a higher risk was found among current smokers (HR: 1.89, 1.19-2.92).MATERIALS AND METHODSWe studied 6,456 nationally representative U.S. respondents with mortality follow-up through to 31 December 2011. Smoking status was assessed by interviews and cotinine levels. Relative leukocyte telomere length (LTL) was quantified by polymerase chain reaction (PCR). Multivariable linear regression was performed to examine LTL by smoking exposure, adjusted for age, sex, race/ethnicity, socioeconomic status, education, body mass index, alcohol consumption, and physical activity. We further estimated the association of LTL with cotinine levels using quantile regression, and with smoking cessation dynamics. Cox regression was used to estimate mortality by smoking status and LTL.ConclusionOur findings indicated a complex association between smoking, telomere length, and mortality. LTL alterations with SHS and smoking cessation warrant further investigation for translation to public health measures.

Highlights

  • Tobacco use is one of the leading global risk factors for mortality, from chronic diseases including heart disease, diabetes and cancer [1, 2]

  • The 90th quantile of leukocyte telomere length (LTL) decreased with increasing cotinine among never smokers, indicating a role of second-hand smoke (SHS)

  • We observed a lower risk of all-cause death for the second quintile compared to the first among never smokers (HR: 0.67, 95% confidence intervals (CIs): 0.52-0.87), and a higher risk was found among current smokers (HR: 1.89, 1.19-2.92)

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Summary

Introduction

Tobacco use is one of the leading global risk factors for mortality, from chronic diseases including heart disease, diabetes and cancer [1, 2]. Www.impactjournals.com/oncotarget recent studies have further focused on mitigating the risk for never smokers as well as former smokers. To this end, understanding the extent of how second-hand smoke (SHS) exposure and smoking cessation affect smokingrelated health outcomes is important to inform public policies. Due to the end-replication problem, each somatic mitotic division results in the loss of telomeric repeats by 30 to 200 base pairs, leading to gradual telomere shortening [6]. Chronic exposure to biological insults such as oxidative stress may result in significantly shortened telomeres which in turn leads to cellular senescence and apoptosis [7, 8]

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