Evidence map›Paper›PMID 28854564›Full record

ArticleHuman molecular genetics2017

Epigenome-wide analysis of DNA methylation in lung tissue shows concordance with blood studies and identifies tobacco smoke-inducible enhancers.

Theresa Ryan Stueve, Wen-Qing Li, Jianxin Shi, Crystal N Marconett, Tongwu Zhang, Chenchen Yang, Daniel Mullen, Chunli Yan, William Wheeler, Xing Hua and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
7.3field-weighted citation impact, top 2% 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

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.

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  9. CYP1B1 Mediates Cigarette Smoke-Induced Lipid Accumulation in Alveolar Type 2 Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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9 more citing papers are in PubMed but not listed here.

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

17 authors at 7 institutions in 3 countries.

Theresa Ryan StueveDepartment of Preventive Medicine.
Wen-Qing LiDivision of Cancer Epidemiology and Genetics, NCI, National Institute of Health, Bethesda, MD 20852, USA.
Jianxin ShiDivision of Cancer Epidemiology and Genetics, NCI, National Institute of Health, Bethesda, MD 20852, USA.
Crystal N MarconettUSC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Tongwu ZhangDivision of Cancer Epidemiology and Genetics, NCI, National Institute of Health, Bethesda, MD 20852, USA.
Chenchen YangUSC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Daniel MullenUSC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Chunli YanUSC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
William WheelerInformation Management Services, Inc., Rockville, MD 20852, USA.
Xing HuaDivision of Cancer Epidemiology and Genetics, NCI, National Institute of Health, Bethesda, MD 20852, USA.
Beiyun ZhouUSC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Zea BorokUSC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Neil E CaporasoDivision of Cancer Epidemiology and Genetics, NCI, National Institute of Health, Bethesda, MD 20852, USA.
Angela C PesatoriUnit of Epidemiology, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Jubao DuanCenter for Psychiatric Genetics, Department of Psychiatry and Behavioral Sciences, North Shore University Health System Research Institute, University of Chicago Pritzker School of Medicine, Evanston, IL 60201, USA.
Ite A Laird-OffringaUSC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Maria Teresa LandiDivision of Cancer Epidemiology and Genetics, NCI, National Institute of Health, Bethesda, MD 20852, USA.
University of Southern California · USDivision of Cancer Epidemiology and GeneticsBrown University · USInformation Management Services · USNorthShore University HealthSystem · USRogers (United States) · USUniversity of Milan · IT

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
Beyond the Barrier: Alveolar Epithelial Cell Biology in Health and DiseaseR35HL135747 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BOROK, ZEA · 2017 to 2023
$6.8M
Systematic Functional Interpretation of Regulatory Variants in SchizophreniaR01MH106575 · NIMH · ENDEAVOR HEALTH CLINICAL OPERATIONS · PI DUAN, JUBAO · 2016 to 2025
$6.1M
Training Grant in Genomic Analysis and InterpretationT32ES013678 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GAUDERMAN, WILLIAM JAMES, MCCONNELL, ROB S · 2006 to 2023
$5.6M
Epigenetic profiling of human alveolar epithelial cells in health and diseaseR01HL114094 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BOROK, ZEA, OFFRINGA, ITE A · 2011 to 2015
$3.3M
Molecular programming of AEC differentiation: role of forkhead factorsR37HL062569 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BOROK, ZEA · 2010 to 2014
$2.2M
Translatome profiling of nicotine addictionR21DA041600 · NIDA · ENDEAVOR HEALTH CLINICAL OPERATIONS · PI DUAN, JUBAO · 2017 to 2018
$449k
NCI NIH HHS P30 CA014089NHLBI NIH HHS R01 HL114094NHLBI NIH HHS R35 HL135747NHLBI NIH HHS R37 HL062569NIDA NIH HHS R21 DA041600NIEHS NIH HHS T32 ES013678NIMH NIH HHS R01 MH106575
6 · The paper itself

Abstract

Smoking-associated DNA hypomethylation has been observed in blood cells and linked to lung cancer risk. However, its cause and mechanistic relationship to lung cancer remain unclear. We studied the association between tobacco smoking and epigenome-wide methylation in non-tumor lung (NTL) tissue from 237 lung cancer cases in the Environment And Genetics in Lung cancer Etiology study, using the Infinium HumanMethylation450 BeadChip. We identified seven smoking-associated hypomethylated CpGs (P < 1.0 × 10-7), which were replicated in NTL data from The Cancer Genome Atlas. Five of these loci were previously reported as hypomethylated in smokers' blood, suggesting that blood-based biomarkers can reflect changes in the target tissue for these loci. Four CpGs border sequences carrying aryl hydrocarbon receptor binding sites and enhancer-specific histone modifications in primary alveolar epithelium and A549 lung adenocarcinoma cells. A549 cell exposure to cigarette smoke condensate increased these enhancer marks significantly and stimulated expression of predicted target xenobiotic response-related genes AHRR (P = 1.13 × 10-62) and CYP1B1 (P < 2.49 × 10-61). Expression of both genes was linked to smoking-related transversion mutations in lung tumors. Thus, smoking-associated hypomethylation may be a consequence of enhancer activation, revealing environmentally-induced regulatory elements implicated in lung carcinogenesis.

Indexed as

A549 CellsBasic Helix-Loop-Helix ProteinsBiomarkers, TumorCpG IslandsCytochrome P-450 CYP1B1DNA MethylationEnhancer Elements, GeneticEpigenesis, GeneticEpigenomicsGenome-Wide Association StudyHumansLungLung NeoplasmsNicotianaRegulatory Sequences, Nucleic AcidRepressor ProteinsAHRR protein, humanBasic Helix-Loop-Helix ProteinsBiomarkers, TumorCYP1B1 protein, humanCytochrome P-450 CYP1B1Repressor Proteins

Identifiers

PMID28854564
PMCPMC5886283
OpenAlexW2614059510

What OpenQuestion holds

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Registered trials

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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.