Agnostic Cys34‐albumin adductomics and DNA methylation: Implication of N‐acetylcysteine in lung carcinogenesis years before diagnosis. Issue 12 (31st October 2019)

• Record Type: Journal Article
• Authors: Dagnino, Sonia; Bodinier, Barbara; Grigoryan, Hasmik; Rappaport, Stephen M.; Karimi, Maryam; Guida, Florence; Polidoro, Silvia; Edmands, WIlliam B.; Naccarati, Alessio; Fiorito, Giovanni; Sacerdote, Carlotta; Krogh, Vittorio; Vermeulen, Roel; Vineis, Paolo; Chadeau‐Hyam, Marc
• Is Part Of: International journal of cancer. Volume 146:Issue 12(2020)
• Page Start: 3294
• Page End: 3303
• Publication Date: 2019-10-31
• Subjects: adductomics -- lung cancer -- DNA‐methylation -- biomarkers -- oxidative stress -- smoking; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.32680
• Languages: English
• ISSNs: 0020-7136

Abstract

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 = 4.15 × 10 −3 ) and of cysteinyl‐glycine ( p = 7.89 × 10 −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. Abstract : What's new? Although smoking and oxidative stress are known contributors to lung carcinogenesis, their action mechanisms remain poorly understood. Here, using human serum albumin Cys‐34 adductomics to gauge exposure to reactive oxygen species, the authors detected for the first time lower levels of N‐acetylcysteine (NAC) adducts in lung cancer cases years before diagnosis. This variation was associated with smoking and hypomethylation at certain smoking‐related CpGs. The results indicate a perturbation in the oxidative stress pathways in future cases and call for further investigation into the role of oxidative stress in lung carcinogenesis and the potential use of NAC as a preventive drug.