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DNA methylation and associated gene expression in blood prior to lung cancer diagnosis in the Norwegian Women and Cancer cohort

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Title: DNA methylation and associated gene expression in blood prior to lung cancer diagnosis in the Norwegian Women and Cancer cohort
Authors: Sandanger, T
Nost, T
Guida, F
Rylander, C
Campanella, G
Muller, D
Van Dongen, J
Boomsma, D
Johansson, M
Vineis, P
Vermeulen, R
Lund, E
Chadeau, M
Item Type: Journal Article
Abstract: The majority of lung cancer is caused by tobacco smoking, and lung cancer-relevant epigenetic markers have been identified in relation to smoking exposure. Still, smoking-related markers appear to mediate little of the effect of smoking on lung cancer. Thus in order to identify disease-relevant markers and enhance our understanding of pathways, a wide search is warranted. Through an epigenome-wide search within a case-control study (131 cases, 129 controls) nested in a Norwegian prospective cohort of women, we found 25 CpG sites associated with lung cancer. Twenty-three were classified as associated with smoking (LC-AwS), and two were classified as unassociated with smoking (LC-non-AwS), as they remained associated with lung cancer after stringent adjustment for smoking exposure using the comprehensive smoking index (CSI): cg10151248 (PC, CSI-adjusted odds ratio (OR) = 0.34 [0.23–0.52] per standard deviation change in methylation) and cg13482620 (B3GNTL1, CSI-adjusted OR = 0.33 [0.22–0.50]). Analysis among never smokers and a cohort of smoking-discordant twins confirmed the classification of the two LC-non-AwS CpG sites. Gene expression profiles demonstrated that the LC-AwS CpG sites had different enriched pathways than LC-non-AwS sites. In conclusion, using blood-derived DNA methylation and gene expression profiles from a prospective lung cancer case-control study in women, we identified 25 CpG lung cancer markers prior to diagnosis, two of which were LC-non-AwS markers and related to distinct pathways.
Issue Date: 13-Nov-2018
Date of Acceptance: 8-Oct-2018
URI: http://hdl.handle.net/10044/1/65308
DOI: https://dx.doi.org/10.1038/s41598-018-34334-6
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 8
Copyright Statement: © 2018 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Italian Institute for Genomic Medicine IIGM
Cancer Research UK
Funder's Grant Number: CG/150
‘Mechanomics’ PRC project grant 22184
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CIGARETTE-SMOKING
BREAST-CANCER
RISK
HYPERMETHYLATION
METAANALYSIS
SIGNATURES
DYNAMICS
PREDICT
CELLS
SERUM
Publication Status: Published
Article Number: 16714
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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