Associations of self-reported smoking, cotinine levels and epigenetic smoking indicators with oxidative stress among older adults: a population-based study

Abstract

Tobacco smoking and oxidative stress (OS) are both related to a wide spectrum of adverse age-related health outcomes, but their association is not yet well-established. We examined the associations of self-reported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with two urinary proxy markers of OS, 8-isoprostane (8-iso) and 8-hydroxy-2'-deoxyguanosine (8-oxodG), in two independent subsets of older adults recruited in Germany (discovery set: n = 978, validation set: n = 531). We obtained DNA methylation profiles in whole blood samples by Illumina Human Methylation450K Beadchip and measured the urinary levels of both OS markers using commercial ELISA kits. After controlling for potential confounders, current smoking, cumulative smoking exposure (pack-years) and serum cotinine levels (ng/ml) were strongly associated with 8-iso levels (p values <0.0001, 0.004 and 0.001, respectively). Of 151 previously identified smoking-related CpG sites, 71 loci were associated with 8-iso levels after correction for multiple testing (FDR < 0.05) in the validation phase and were designated as loci related to 8-iso levels defined OS. In addition, serum cotinine levels, cumulative smoking exposure and a smoking index (SI) based on the 71 identified loci manifested monotonic associations with 8-iso levels. However, we did not observe any associations between these smoking indicators and 8-oxodG levels. In conclusion, this study suggests that smoking-related epigenetic alterations are closely correlated with smoking-induced OS. The identified CpG sites could potentially be prognostic epigenetic markers of OS and OS-related health outcomes. Our findings and the underlying mechanisms should be followed up in further, preferably longitudinal studies.

Pre‐diagnostic derivatives of reactive oxygen metabolites and the occurrence of lung, colorectal, breast and prostate cancer: An individual participant data meta‐analysis of two large population‐based studies

“…If the d‐ROM test was conducted in this context, it may be used to motivate individuals with increased serum d‐ROM levels >340 Carr U (threshold for increased all‐cause mortality) to change their lifestyle. Although clinical trials are needed in this research area, many studies suggest that smoking cessation, a low‐caloric diet and an increase in regularly performed physical activity of moderate intensity can reduce oxidative stress . In agreement with the cited studies, we observed increased d‐ROM levels in both the ESTHER and the Tromsø study in current smokers, obese individuals and physical inactive study participants.…”

Leukocyte telomere length and epigenetic-based mortality risk score: associations with all-cause mortality among older adults

“…As shown in Figure 3, 9949 older adults (aged 50-75 years) were enrolled by their general practitioners during a routine health checkup between July 2000 and December 2002, and followed up thereafter. The cross-sectional analysis of this study is based on the data and biospecimen of two subgroups collected at baseline, from 1517 participants (N group 1 = 975 and N group 2 = 542) who were randomly selected for the measurements of DNA methylation and TL among participants recruited consecutively at the start of the ESTHER study from July 2000 to October 2000 (group1) and from October 2000 to March 2001 (group2) [40]. The selected participants were then regularly followed up with respect to the incidence of major chronic diseases and mortality.…”

“…Information on socio-demographic characteristics, lifestyle factors and health status at baseline was obtained by standardized self-administered questionnaires [40]. Participants were asked about their past and present smoking behaviors and were then categorized into current, former and never smokers.…”

“…DNA methylation profiles were determined by the Illumina HumanMethylation450K Beadchip (Illumina, San Diego, CA, USA). As previously described [40], samples of the two subgroups were seperately analyzed following the manufacturer's instruction at the Genomics and Proteomics Core Facility of the German Cancer Research Center, Heidelberg, Germany. Illumina's GenomeStudio® (version 2011.1; Illumina.Inc.)…”

Naringin Reveals Ameliorative Property Over Elevated Oxidative Stress Levels in Animal Models

“…The reactive oxygen metabolites produced are more reactive than the original oxygen molecule and are called active oxygen species. Many daily habits are closely associated with OxiS which includes smoking [2][3][4][5], drinking [6][7][8][9], and an irregular diet [10][11][12][13]. The superoxide radical (·O 2ˉ) , one of the reactive oxygen species (ROS), is known to be generated in brain and is involved in the reduction of certain iron complexes including cytochrome C. Superoxide dismutase is a metalloenzyme catalytically eliminating superoxide radical as a first-line defense mechanism against OxiS [14].…”