TY - JOUR
T1 - Epigenetic mechanisms of lung carcinogenesis involve differentially methylated CpG sites beyond those associated with smoking
AU - Petrovic, Dusan
AU - Bodinier, Barbara
AU - Dagnino, Sonia
AU - Whitaker, Matthew
AU - Karimi, Maryam
AU - Campanella, Gianluca
AU - Haugdahl Nøst, Therese
AU - Polidoro, Silvia
AU - Palli, Domenico
AU - Krogh, Vittorio
AU - Tumino, Rosario
AU - Sacerdote, Carlotta
AU - Panico, Salvatore
AU - Lund, Eiliv
AU - Dugué, Pierre Antoine
AU - Giles, Graham G.
AU - Severi, Gianluca
AU - Southey, Melissa
AU - Vineis, Paolo
AU - Stringhini, Silvia
AU - Bochud, Murielle
AU - Sandanger, Torkjel M.
AU - Vermeulen, Roel C.H.
AU - Guida, Florence
AU - Chadeau-Hyam, Marc
N1 - Funding Information:
This work was supported by Cancer Research UK Population Research Committee ‘Mechanomics’ project Grant (Grant #22184 to MC-H). The NOWAC post-genome cohort study was funded by the ERC advanced Grant; Transcriptomics in Cancer Epidemiology (ERC-2008-AdG-232997). MC-H, FG, KS-B, THN, MJ, and TS acknowledge support from the Research Council of Norway (Id-Lung project FRIPRO 262111 to TS). MC-H, RV, acknowledge support from the H2020-EXPANSE project (Horizon 2020 Grant No 874627 to RV). SD acknowledges support to Horizon 2020 Marie Skłodowska-Curie fellowship EXACT Identifying biomarkers of EXposure leading to Lung Cancer with AdduCTomics (Grant # 708392 to SD). DP was supported by a Grant from the Swiss National Science Foundation (SNSF DocMobility Grant P1LAP3_178061). BB received a PhD studentship from the MRC Centre for Environment and Health.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - DNA methylation
KW - Lung cancer
KW - Partial correlation network
KW - Smoking
KW - Variable selection
UR - https://www.scopus.com/pages/publications/85130295207
U2 - 10.1007/s10654-022-00877-2
DO - 10.1007/s10654-022-00877-2
M3 - Article
C2 - 35595947
AN - SCOPUS:85130295207
SN - 0393-2990
VL - 37
SP - 629
EP - 640
JO - European Journal of Epidemiology
JF - European Journal of Epidemiology
ER -