期刊
SCIENTIFIC REPORTS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-34334-6
关键词
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资金
- European Research Council (ERC)
- Identifying biomarkers of metastatic lung cancer using gene expression, DNA methylation and miRNA in blood prior to clinical diagnosis (RCN, FRIMEDBIO) [262111]
- Identifying biomarkers of metastatic lung cancer using gene expression, DNA methylation and miRNA in blood prior to clinical diagnosis (Norwegian Cancer Society)
- Cancer Research-UK 'Mechanomics' PRC project grant [PRC 22184]
- National Cancer Institute [U19 CA148127 02]
- Biobanking and Biomolecular Resources Research Infrastructure [BBRMI 184.021.007]
- Royal Netherlands Academy of Science Professor Award [PAH/6635]
- NATIONAL CANCER INSTITUTE [U19CA148127] Funding Source: NIH RePORTER
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.
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