Objectives The aim of our study is to validate and complement recently reported epigenetic biomarkers of exposure to tobacco smoke based on data from two cohorts and to characterise their prospective nature.
Method We used case-control data from studies nested in two prospective cohorts: the Italian component of the European Prospective Investigation into Cancer and Nutrition study (N = 620) and the Norwegian Women and Cancer study (N = 382) as a validation dataset. For each of the participant, genome wide methylation profiles were acquired from blood samples collected at enrolment using the Illumina HM450 DNA methylation array. We performed epigenome wide association studies within each dataset to assess the relation between methylation levels and smoking-related variables, controlling for technical variation (batch effects) and confounding factors (including white blood cell composition).
Results We found 8 and 897 CpG sites differentially methylated in former and current smokers, while compared to never smokers, respectively. The 8 candidate markers of former smoking showed a gradual reversion of their methylation levels from those typical of current smokers to those of never smokers. Further analyses using cumulative (over varying time windows) smoking intensities, highlighted three classes of biomarkers: short and long term biomarkers (measuring the effect of smoking in the past 10, and in the past 10 to 30 years respectively), and lifelong biomarkers detected more than 30 years after quitting smoking.
Conclusions Genome-wide DNA methylation profiles show promising abilities to detect short-term to lifelong biomarkers of tobacco smoke exposure and, more generally, to potentially identify time-varying biomarkers of exposure.
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