Epigenetic mechanisms of lung carcinogenesis involve differentially methylated CpG sites beyond those associated with smoking.
DNA methylation
Lung cancer
Partial correlation network
Smoking
Variable selection
Journal
European journal of epidemiology
ISSN: 1573-7284
Titre abrégé: Eur J Epidemiol
Pays: Netherlands
ID NLM: 8508062
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
28
09
2021
accepted:
25
04
2022
pubmed:
21
5
2022
medline:
20
7
2022
entrez:
20
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35595947
doi: 10.1007/s10654-022-00877-2
pii: 10.1007/s10654-022-00877-2
pmc: PMC9288379
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
629-640Subventions
Organisme : Cancer Research UK
ID : 22184
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S019669/1
Pays : United Kingdom
Organisme : European Research Council
ID : ERC-2008-AdG-232997
Pays : International
Informations de copyright
© 2022. The Author(s).
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