Evidence map›Paper›PMID 24671036›Full record

ArticleEpigenetics2014

Leukocyte-adjusted epigenome-wide association studies of blood from solid tumor patients.

Scott M Langevin, E Andres Houseman, William P Accomando, Devin C Koestler, Brock C Christensen, Heather H Nelson, Margaret R Karagas, Carmen J Marsit, John K Wiencke, Karl T Kelsey

Abstract read
In one paragraph

Article in Epigenetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

18 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  4. The association betweenFrontiers in cardiovascular medicine · 2022
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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

10 authors.

Scott M LangevinDepartment of Environmental Health; University of Cincinnati College of Medicine; Cincinnati, OH USA; Department of Epidemiology; Brown University; Providence, RI USA.
E Andres HousemanDepartment of Biostatistics; Oregon State University College of Public Health and Human Sciences; Corvallis, OR USA.
William P AccomandoDepartment of Pathology & Laboratory Medicine; Brown University; Providence, RI USA.
Devin C KoestlerDepartment of Community and Family Medicine; Section of Biostatistics and Epidemiology; Dartmouth Medical School; Lebanon, NH USA.
Brock C ChristensenDepartment of Community and Family Medicine; Section of Biostatistics and Epidemiology; Dartmouth Medical School; Lebanon, NH USA; Department of Pharmacology and Toxicology; Dartmouth Medical School; Lebanon, NH USA.
Heather H NelsonDivision of Epidemiology and Community Health; University of Minnesota Masonic Cancer Center; Minneapolis, MN USA.
Margaret R KaragasDepartment of Community and Family Medicine; Section of Biostatistics and Epidemiology; Dartmouth Medical School; Lebanon, NH USA.
Carmen J MarsitDepartment of Community and Family Medicine; Section of Biostatistics and Epidemiology; Dartmouth Medical School; Lebanon, NH USA; Department of Pharmacology and Toxicology; Dartmouth Medical School; Lebanon, NH USA.
John K WienckeDepartment of Neurological Surgery; University of California San Francisco; San Francisco, CA USA.
Karl T KelseyDepartment of Epidemiology; Brown University; Providence, RI USA; Department of Pathology & Laboratory Medicine; Brown University; Providence, RI USA.

Funding

VARIATION IN BIOACCUMULATION AND BIOMAGNIFICATION OF METALS IN NORTHERN US LAKESP42ES007373 · NIEHS · DARTMOUTH COLLEGE · PI BORSUK, MARK EDWARD · 1995 to 2019
$52.0M
NONMELANOMA SKIN CANCER IN NEW HAMPSHIRER01CA057494 · NCI · DARTMOUTH COLLEGE · PI KARAGAS, MARGARET RITA · 1993 to 2015
$10.9M
TRAINING IN ENVIRONMENTAL PATHOLOGYT32ES007272 · NIEHS · BROWN UNIVERSITY · PI ZHITKOVICH, ANATOLY · 1992 to 2021
$7.5M
The Boston Collaborative Oral Cancer StudyR01CA078609 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI KELSEY, KARL TIMOTHY · 1999 to 2010
$5.3M
MOLECULAR EPIDEMIOLOGY OF NON-MELANOMA SKIN CANCERR01CA082354 · NCI · UNIVERSITY OF MINNESOTA · PI NELSON, HEATHER HAMMOND · 1999 to 2011
$4.2M
Patterns of Somatic Gene Alterations in Oral CancerR01CA100679 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI KELSEY, KARL TIMOTHY · 2004 to 2012
$2.6M
Biomarkers of survival in glioma epidemiologyR01CA126831 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WIENCKE, JOHN K. · 2008 to 2013
$2.5M
The Molecular Epidemiology of Bladder CancerR01CA121147 · NCI · BROWN UNIVERSITY · PI KELSEY, KARL TIMOTHY · 2007 to 2010
$2.0M
Epigenetic alterations in oral rinse as biomarkers of oral and pharyngeal cancerK22CA172358 · NCI · UNIVERSITY OF CINCINNATI · PI LANGEVIN, SCOTT M. · 2013 to 2015
$312k
NCI NIH HHS K22 CA172358NCI NIH HHS K22CA172358NCI NIH HHS R01 CA057494NCI NIH HHS R01CA057494NCI NIH HHS R01 CA078609NCI NIH HHS R01CA078609NCI NIH HHS R01 CA082354NCI NIH HHS R01CA082354NCI NIH HHS R01 CA100679NCI NIH HHS R01CA100679NCI NIH HHS R01 CA121147NCI NIH HHS R01CA121147NCI NIH HHS R01 CA126831NCI NIH HHS R01CA126831NIEHS NIH HHS P42 ES007373NIEHS NIH HHS P42ES007373NIEHS NIH HHS T32 ES007272NIEHS NIH HHS T32ES07272
6 · The paper itself

Abstract

Epigenome-wide studies of DNA methylation using blood-derived DNA from cancer patients are complicated by the heterogeneity of cell types within blood and the associated cell lineage specification of DNA methylation signatures. Here, we applied a novel set of analytic approaches to assess the association between cancer case-status and DNA methylation adjusted for leukocyte variation using blood specimens from three case-control cancer studies (bladder: 223 cases, 205 controls; head and neck: 92 cases, 92 controls; and ovarian: 131 cases, 274 controls). Using previously published data on leukocyte-specific CpG loci and a recently described approach to deconvolute subject-specific blood composition, we performed an epigenome-wide analysis to examine the association between blood-based DNA methylation patterns and each of the three aforementioned solid tumor types adjusted for cellular heterogeneity in blood. After adjusting for leukocyte profile in our epigenome-wide analysis, the omnibus association between case-status and methylation was significant for all three studies (bladder cancer: P = 0.047; HNSCC: P = 0.013; ovarian cancer: P = 0.0002). Subsequent analyses revealed that CpG sites associated with cancer were enriched for transcription factor binding motifs involved with cancer-associated pathways. These results support the existence of cancer-associated DNA methylation profiles in the blood of solid tumor patients that are independent of alterations in normal leukocyte distributions. Adoption of the methods developed here will make it feasible to rigorously assess the influence of variability of normal leukocyte profiles when investigating cancer related changes in blood-based epigenome-wide association studies.

Indexed as

Epigenesis, GeneticAdultAgedAged, 80 and overCase-Control StudiesCpG IslandsDNA MethylationFemaleGenome-Wide Association StudyHead and Neck NeoplasmsHumansLeukocytesMaleMiddle AgedOvarian NeoplasmsRegulatory Sequences, Nucleic Acidbladder cancerepigenomicsEWASHNSCCovarian cancer

Identifiers

PMID24671036
PMCPMC4065186

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.