Evidence map›Paper›PMID 33729499›Full record

ArticleInternational journal of epidemiology2021

Assessing the role of genome-wide DNA methylation between smoking and risk of lung cancer using repeated measurements: the HUNT study.

Yi-Qian Sun, Rebecca C Richmond, Matthew Suderman, Josine L Min, Thomas Battram, Arnar Flatberg, Vidar Beisvag, Therese Haugdahl Nøst, Florence Guida, Lin Jiang and 11 more

Open access · hybridAbstract read
In one paragraph

Article in International journal of epidemiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.

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  14. Smoking, blood DNA methylation sites and lung cancer risk.Environmental pollution (Barking, Essex : 1987) · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 8 institutions in 5 countries.

Yi-Qian SunDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.ORCID 0000-0002-9634-9236
Rebecca C RichmondMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0003-0574-5071
Matthew SudermanMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Josine L MinMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Thomas BattramMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Arnar FlatbergDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Vidar BeisvagDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Therese Haugdahl NøstDepartment of Community Medicine, Faculty of Health Sciences, Arctic University of Norway, Tromsø, Norway.
Florence GuidaGenetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
Lin JiangDepartment of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Sissel Gyrid Freim WahlDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Arnulf LanghammerHUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Frank SkorpenDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Rosie M WalkerCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Andrew D BretherickMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Yanni ZengFaculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Yue ChenSchool of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Mattias JohanssonGenetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
Torkjel M SandangerDepartment of Community Medicine, Faculty of Health Sciences, Arctic University of Norway, Tromsø, Norway.
Caroline L ReltonMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Xiao-Mei MaiDepartment of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Norwegian University of Science and Technology · NOUniversity of Bristol · GBCentre international de recherche sur le cancer · FRSun Yat-sen University · CNUiT The Arctic University of Norway · NOUniversity of Edinburgh · GBUniversity of Ottawa · CAWestern General Hospital · GB

Funding

Cancer Research UK 19169Cancer Research UK 22171Cancer Research UK 29019Medical Research Council MC_UU_00011/5Wellcome TrustWorld Health Organization 001
6 · The paper itself

Abstract

backgroundIt is unclear if smoking-related DNA methylation represents a causal pathway between smoking and risk of lung cancer. We sought to identify novel smoking-related DNA methylation sites in blood, with repeated measurements, and to appraise the putative role of DNA methylation in the pathway between smoking and lung cancer development.

methodsWe derived a nested case-control study from the Trøndelag Health Study (HUNT), including 140 incident patients who developed lung cancer during 2009-13 and 140 controls. We profiled 850 K DNA methylation sites (Illumina Infinium EPIC array) in DNA extracted from blood that was collected in HUNT2 (1995-97) and HUNT3 (2006-08) for the same individuals. Epigenome-wide association studies (EWAS) were performed for a detailed smoking phenotype and for lung cancer. Two-step Mendelian randomization (MR) analyses were performed to assess the potential causal effect of smoking on DNA methylation as well as of DNA methylation (13 sites as putative mediators) on risk of lung cancer.

resultsThe EWAS for smoking in HUNT2 identified associations at 76 DNA methylation sites (P < 5 × 10-8), including 16 novel sites. Smoking was associated with DNA hypomethylation in a dose-response relationship among 83% of the 76 sites, which was confirmed by analyses using repeated measurements from blood that was collected at 11 years apart for the same individuals. Two-step MR analyses showed evidence for a causal effect of smoking on DNA methylation but no evidence for a causal link between DNA methylation and the risk of lung cancer.

conclusionsDNA methylation modifications in blood did not seem to represent a causal pathway linking smoking and the lung cancer risk.

Indexed as

DNA MethylationLung NeoplasmsCase-Control StudiesCpG IslandsDNAEpigenesis, GeneticGenome-Wide Association StudyHumansSmokingDNACausal inferenceEWASMendelian randomization

Identifiers

PMID33729499
PMCPMC8580278
OpenAlexW3136853350

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.