Epigenetic mechanisms of lung carcinogenesis involve differentially methylated CpG sites beyond those associated with smoking

Dusan Petrovic, Barbara Bodinier, Sonia Dagnino, Matthew Whitaker, Maryam Karimi, Gianluca Campanella, Therese Haugdahl Nøst, Silvia Polidoro, Domenico Palli, Vittorio Krogh, Rosario Tumino, Carlotta Sacerdote, Salvatore Panico, Eiliv Lund, Pierre Antoine Dugué, Graham G. Giles, Gianluca Severi, Melissa Southey, Paolo Vineis, Silvia StringhiniMurielle Bochud, Torkjel M. Sandanger, Roel C.H. Vermeulen, Florence Guida, Marc Chadeau-Hyam

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

Smoking-related epigenetic changes have been linked to lung cancer, but the contribution of epigenetic alterations unrelated to smoking remains unclear. We sought for a sparse set of CpG sites predicting lung cancer and explored the role of smoking in these associations. We analysed CpGs in relation to lung cancer in participants from two nested case–control studies, using (LASSO)-penalised regression. We accounted for the effects of smoking using known smoking-related CpGs, and through conditional-independence network. We identified 29 CpGs (8 smoking-related, 21 smoking-unrelated) associated with lung cancer. Models additionally adjusted for Comprehensive Smoking Index-(CSI) selected 1 smoking-related and 49 smoking-unrelated CpGs. Selected CpGs yielded excellent discriminatory performances, outperforming information provided by CSI only. Of the 8 selected smoking-related CpGs, two captured lung cancer-relevant effects of smoking that were missed by CSI. Further, the 50 CpGs identified in the CSI-adjusted model complementarily explained lung cancer risk. These markers may provide further insight into lung cancer carcinogenesis and help improving early identification of high-risk patients.

Lingua originaleInglese
pagine (da-a)629-640
Numero di pagine12
RivistaEuropean Journal of Epidemiology
Volume37
Numero di pubblicazione6
DOI
Stato di pubblicazionePubblicato - giu 2022
Pubblicato esternamente

Fingerprint

Entra nei temi di ricerca di 'Epigenetic mechanisms of lung carcinogenesis involve differentially methylated CpG sites beyond those associated with smoking'. Insieme formano una fingerprint unica.

Cita questo