Epigenetic mechanisms of lung carcinogenesis involve differentially methylated CpG sites beyond those associated with smoking
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https://hdl.handle.net/10037/26449Date
2022-05-20Type
Journal articleTidsskriftartikkel
Peer reviewed
Author
Petrovic, Dusan; Bodinier, Barbara; Dagnino, Sonia; Whitaker, Matthew; Karimi, Maryam; Campanella, Gianluca; Nøst, Therese Haugdahl; Polidoro, Silvia; Palli, Domenico; Krogh, Vittorio; Tumino, Rosario; Sacerdote, Carlotta; Panico, Salvatore; Lund, Eiliv; Dugué, Pierre-Antoine; Giles, Graham G; Severi, Gianluca; Southey, Melissa; Vineis, Paolo; Stringhini, Silvia; Bochud, Murielle; Sandanger, Torkjel M; Vermeulen, Roel CH; Guida, Florence; Chadeau-Hyam, MarcAbstract
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 efects of smoking using known smoking-related CpGs, and through
conditional-independence network. We identifed 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 smokingunrelated 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 efects of smoking that were missed by
CSI. Further, the 50 CpGs identifed in the CSI-adjusted model complementarily explained lung cancer risk. These markers
may provide further insight into lung cancer carcinogenesis and help improving early identifcation of high-risk patients.
Publisher
SpringerCitation
Petrovic, Bodinier, Dagnino, Whitaker, Karimi, Campanella, Nøst, Polidoro, Palli, Krogh, Tumino, Sacerdote, Panico, Lund, Dugué, Giles, Severi, Southey, Vineis, Stringhini, Bochud, Sandanger, Vermeulen, Guida, Chadeau-Hyam. Epigenetic mechanisms of lung carcinogenesis involve differentially methylated CpG sites beyond those associated with smoking. European Journal of Epidemiology (EJE). 2022Metadata
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