Research Papers:

Smoking, second-hand smoke exposure and smoking cessation in relation to leukocyte telomere length and mortality

Wahyu Wulaningsih _, Fidel Emmanuel C. Serrano, Adi Utarini, Tetsuya Matsuguchi, Johnathan Watkins and for PILAR Research Network

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Oncotarget. 2016; 7:60419-60431. https://doi.org/10.18632/oncotarget.11051

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Wahyu Wulaningsih1,2,3,4, Fidel Emmanuel C. Serrano5, Adi Utarini6, Tetsuya Matsuguchi7,8, Johnathan Watkins4,9, for PILAR Research Network

1Division of Cancer Studies, King’s College London, London, UK

2MRC Unit for Lifelong Health and Ageing, University College London, London, UK

3Division of Haematology/Oncology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

4PILAR Research and Education, Cambridge, UK

5National Institute of Molecular Biology and Biotechnology, University of The Philippines Diliman, Diliman, Quezon City, Metro Manila, The Philippines

6Department of Health Policy and Management, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

7Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA

8Driver Group, L.L.C., San Francisco, CA, USA

9Institute for Mathematical and Molecular Biomedicine, King’s College London, London, UK

Correspondence to:

Wahyu Wulaningsih, email: [email protected]

Keywords: smoking, second-hand smoke exposure, smoking cessation, telomere, ageing

Received: May 27, 2016    Accepted: July 19, 2016    Published: August 4, 2016


Objectives: To investigate the link between smoking exposure, telomere length and mortality, with emphasis on second-hand smoke (SHS) exposure and the duration of smoking cessation.

Results: A 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 Methods: We 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.

Conclusion: Our 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.

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