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

Torkjel Manning Sandanger*, Therese Haugdahl Nøst, Florence Guida, Charlotta Rylander, Gianluca Campanella, David C. Muller, Jenny van Dongen, Dorret I. Boomsma, Mattias Johansson, Paolo Vineis, Roel Vermeulen, Eiliv Lund, Marc Chadeau-Hyam

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Article number16714
Pages (from-to)1-10
Number of pages10
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 13 Nov 2018

Funding

The author acknowledge the study participants and the technical assistance of the associated biobanks. This work was supported by European Research Council (ERC), Advanced Researcher Grant, 2008: Transcriptomics in cancer research (TICE); Identifying biomarkers of metastatic lung cancer using gene expression, DNA methylation and miRNA in blood prior to clinical diagnosis (RCN, FRIMEDBIO grant numer 262111 and the Norwegian Cancer Society); Cancer Research -UK ‘Mechanomics’ PRC project grant (grant number PRC 22184) to MC-H; MC-H and PV also acknowledge the Transdisciplinary Research in Cancer of the Lung (TRICL) project which is supported by the National Cancer Institute (grant number U19 CA148127 02 to Chris Amos); Biobanking and Biomolecular Resources Research Infrastructure (grant number BBRMI 184.021.007); and Royal Netherlands Academy of Science Professor Award (grant number PAH/6635 to DIB).

FundersFunder number
Biobanking and Biomolecular Resources Research InfrastructureBBRMI 184.021.007
Cancer Research -UK ‘MechanomicsPRC 22184
Royal Netherlands Academy of SciencePAH/6635
National Cancer InstituteU19CA148127
Kreftforeningen
European Research Council262111

    Cohort Studies

    • Netherlands Twin Register (NTR)

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