Agnostic Cys34-albumin adductomics and DNA methylation: implication of Nacetylcysteine in lung carcinogenesis years before diagnosis
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Although smoking and oxidative stress are known contributors to lung carcinogenesis, their
mechanisms of action remain poorly understood. To shed light into these mechanisms, we
applied a novel approach using Cys34-adductomics in a lung cancer nested case-control
study (n=212). Adductomics profiles were integrated with DNA-methylation data at
established smoking-related CpG sites measured in the same individuals. Our analysis
identified 42 Cys34-albumin adducts, of which 2 were significantly differentially abundant in
cases and controls: adduct of N-acetylcysteine (NAC, p=4.15x10-3) and of Cysteinyl-Glycine
(Cys-Gly, p=7.89x10-3). Blood levels of the former were found associated to the methylation
levels at 11 smoking related CpG sites. We detect, for the first time in prospective blood
samples, and irrespective of time-to-diagnosis, decreased levels of NAC adduct in lung
cancer cases. Altogether, our results highlight the potential role of these adducts in the
oxidative stress response contributing to lung carcinogenesis years before diagnosis.
mechanisms of action remain poorly understood. To shed light into these mechanisms, we
applied a novel approach using Cys34-adductomics in a lung cancer nested case-control
study (n=212). Adductomics profiles were integrated with DNA-methylation data at
established smoking-related CpG sites measured in the same individuals. Our analysis
identified 42 Cys34-albumin adducts, of which 2 were significantly differentially abundant in
cases and controls: adduct of N-acetylcysteine (NAC, p=4.15x10-3) and of Cysteinyl-Glycine
(Cys-Gly, p=7.89x10-3). Blood levels of the former were found associated to the methylation
levels at 11 smoking related CpG sites. We detect, for the first time in prospective blood
samples, and irrespective of time-to-diagnosis, decreased levels of NAC adduct in lung
cancer cases. Altogether, our results highlight the potential role of these adducts in the
oxidative stress response contributing to lung carcinogenesis years before diagnosis.
Date Issued
2020-06-15
Date Acceptance
2019-08-19
Citation
International Journal of Cancer, 2020, 146 (12), pp.3294-3303
ISSN
0020-7136
Publisher
Wiley
Start Page
3294
End Page
3303
Journal / Book Title
International Journal of Cancer
Volume
146
Issue
12
Sponsor
Commission of the European Communities
Cancer Research UK
Medical Research Council
Research Executive Agency
Grant Number
308610
‘Mechanomics’ PRC project grant 22184
MR/L019744/1
708392
Subjects
DNA-methylation
adductomics
biomarkers
lung cancer
oxidative stress
smoking
Oncology & Carcinogenesis
1112 Oncology and Carcinogenesis
Publication Status
Published
Date Publish Online
2020-09-12