Effects of cigarette smoking and nicotine metabolite ratio on leukocyte telomere length

Environ Res. 2015 Jul:140:488-94. doi: 10.1016/j.envres.2015.05.008. Epub 2015 May 18.


Studies of the effects of smoking on leukocyte telomere length (LTL) using cigarettes smoked per day or pack years smoked (PYS) present limitations. Reported high levels of smoking may not increase toxin exposure levels proportionally. Nicotine metabolism ratio (NMR) predicts total cigarette puff volume and overall exposure based on total N-nitrosamines, is highly reproducible and independent of time since the last cigarette. We hypothesized that smokers with higher NMRs will exhibit increased total puff volume, reflecting efforts to extract more nicotine from their cigarettes and increasing toxin exposure. In addition, higher levels of smoking could cause a gross damage in LTL. The urinary cotinine, 3-OH cotinine and nicotine levels of 147 smokers were analyzed using a LC/MS system Triple-Q6410. LTL and CYP2A6 genotype was determined by PCR in blood samples. We found a significant association between NMR and CYP2A6 genotype. Reduction in LTL was seen in relation to accumulated tobacco consumption and years smoking when we adjusted for age and gender. However, there were no significant differences between NMR values and LTL. In our study the higher exposure was associated with lower number of PYS. Smokers with reduced cigarette consumption may exhibit compensatory smoking behavior that results in no reduced tobacco toxin exposure. Our results suggest that lifetime accumulated smoking exposure could cause a gross damage in LTL rather than NMR or PYS. Nevertheless, a combination of smoking topography (NMR) and consumption (PYS) measures may provide useful information about smoking effects on health outcomes.

Keywords: 3-OH-cotinine; CYP2A6; Cotinine; Leukocyte telomere length; NMR; Nicotine; Pack years smoked.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / urine
  • Cytochrome P-450 CYP2A6 / genetics
  • Humans
  • Leukocytes / ultrastructure*
  • Nicotiana*
  • Nicotine / metabolism*
  • Smoking*
  • Telomere*


  • Biomarkers
  • Nicotine
  • CYP2A6 protein, human
  • Cytochrome P-450 CYP2A6