Evidence map›Paper›PMID 33300568›Full record

Observational studyCarcinogenesis2021

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

Shruti G Dighe, Jianhong Chen, Li Yan, Qianchuan He, Puya Gharahkhani, Lynn Onstad, David M Levine, Claire Palles, Weimin Ye, Marilie D Gammon and 63 more

Open access · greenAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Carcinogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.2field-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

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Pathogenesis of Barrett's Esophagus: Evolving and Emerging Mechanisms.Gastrointestinal endoscopy clinics of North America · 2026
    Review
  2. Article
  3. Article
  4. Mechanisms and pathophysiology of Barrett oesophagus.Nature reviews. Gastroenterology & hepatology · 2022
    Review
  5. Article
  6. Contribution ofPharmacogenomics and personalized medicine · 2022
    Article
  7. Article
  8. Review
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

73 authors at 20 institutions in 7 countries.

Shruti G DigheDepartment of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Jianhong ChenDepartment of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Li YanDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Qianchuan HeDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Puya GharahkhaniStatistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Lynn OnstadDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
David M LevineDepartment of Biostatistics, University of Washington, School of Public Health, Seattle, WA, USA.
Claire PallesGastrointestinal Cancer Genetics Laboratory, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Weimin YeDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Marilie D GammonDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
Prasad G IyerDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Lesley A AndersonDepartment of Epidemiology and Public Health, Queen's University of Belfast, Royal Group of Hospitals, Belfast, UK.
Geoffrey LiuDepartment of Pharmacogenomic Epidemiology, Ontario Cancer Institute, Toronto, Ontario, Canada.
Anna H WuDepartment of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
James Y DaiDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Wong-Ho ChowDepartment of Epidemiology, MD Anderson Cancer Center, Houston, TX, USA.
Harvey A RischDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
Jesper LagergrenDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Nicholas J ShaheenDivision of Gastroenterology and Hepatology, University of North Carolina School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Leslie BernsteinDepartment of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Douglas A CorleyDivision of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Hans PrenenOncology Department, University Hospital Antwerp, Edegem, Belgium.
John deCaesteckerDigestive Diseases Centre, University Hospitals of Leicester, Leicester, UK.
David MacDonaldDepartment of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Paul MoayyediFarncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Hugh BarrDepartment of Upper GI Surgery, Gloucestershire Royal Hospital, Gloucester, UK.
Sharon B LoveCentre for Statistics in Medicine, University of Oxford, Oxford, UK; MRC Clinical Trials Unit at University College London, London, UK.
Laura ChegwiddenUniversity of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Stephen AttwoodDepartment of General Surgery, North Tyneside General Hospital, North Shields, UK.
Peter WatsonDepartment of Medicine, Institute of Clinical Science, Royal Victoria Hospital, Belfast, UK.
Rebecca HarrisonDepartment of Pathology, Leicester Royal Infirmary, Leicester, UK.
Katja OttDepartment of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
Susanne MoebusBiometry and Epidemiology, Institute for Urban Public Health, University Hospitals, University of Duisburg-Essen, Essen, Germany.
Marino VeneritoDepartment of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.
Hauke LangDepartment of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany.
Rupert MayershoferGastroenterologie am Burgweiher, Bonn, Germany.
Michael KnappInstitute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Germany.
Lothar VeitsInstitute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
Christian GergesDepartment of Internal Medicine, Evangelisches Krankenhaus, Düsseldorf, Germany.
Josef WeismüllerGastroenterologische Gemeinschaftspraxis, Koblenz, Germany.
Ines GockelDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
Yogesh VashistDepartment of Surgery, Asklepios Harzklinik Goslar, Goslar, Germany.
Markus M NöthenInstitute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.
Jakob R IzbickiGeneral, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Hendrik MannerDepartment of Internal Medicine II, Frankfurt Hoechst Hospital, Frankfurt, Germany.
Horst NeuhausDepartment of Internal Medicine, Evangelisches Krankenhaus, Düsseldorf, Germany.
Thomas RöschDepartment of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Anne C BöhmerInstitute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.
Arnulf H HölscherClinic for General, Visceral and Trauma Surgery, Department of Surgery, Contilia Center for Esophageal Diseases. Elisabeth Hospital, Essen, Germany.
Mario AndersDepartment of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Oliver PechDepartment of Gastroenterology and Interventional Endoscopy, St. John of God Hospital, Regensburg, Germany.
Brigitte SchumacherDepartment of Internal Medicine, Evangelisches Krankenhaus, Düsseldorf, Germany.
Claudia SchmidtDepartment of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
Thomas SchmidtDepartment of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
Tania NoderDepartment of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Dietmar LorenzDepartment of General and Visceral Surgery, Sana Klinikum, Offenbach, Germany.
Michael ViethInstitute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
Andrea MayDepartment of Gastroenterology, Oncology and Pneumology, Asklepios Paulinen Klinik, Wiesbaden, Germany.
Timo HessCenter for Human Genetics, University Hospital of Marburg, Marburg, Germany.
Nicole KreuserDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
Jessica BeckerInstitute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.
Christian EllDepartment of Medicine II, Sana Klinikum, Offenbach, Germany.
Christine B AmbrosoneDepartment of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Kirsten B MoysichDepartment of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Stuart MacGregorStatistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Ian TomlinsonGastrointestinal Cancer Genetics Laboratory, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
David C WhitemanCancer Control, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Janusz JankowskiDivision of Medicine Kings Mill Hospital, Sherwood Hospitals NHS Trust, Nottinghamshire, UK.
Johannes SchumacherCenter for Human Genetics, University Hospital of Marburg, Marburg, Germany.
Thomas L VaughanDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Margaret M MadeleineDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Laura J HardieDepartment of Epidemiology, University of Leeds, Leeds, UK.
Matthew F BuasDepartment of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Roswell Park Comprehensive Cancer Center · USUniversität Hamburg · DEUniversity of Bonn · DEFred Hutch Cancer Center · USQIMR Berghofer Medical Research Institute · AUUniversity of Washington · USBayreuth Medical Center · DEElisabeth-Krankenhaus Essen · DEEvangelisches Krankenhaus Düsseldorf · DEHeidelberg University · DEPhilipps University of Marburg · DESana Klinikum Offenbach · DEUniversity Hospital Leipzig · DEUniversity of Birmingham · GBUniversity of North Carolina at Chapel Hill · USUniversity of Ulster · GBAntwerp University Hospital · BEAsklepios · DEAsklepios Fachklinikum Brandenburg · DECity of Hope · US

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI Dean G. Tang · 1985 to 2026
$116.6M
Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study (BEAGESS)R01CA136725 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI VAUGHAN, THOMAS L, WHITEMAN, DAVID C · 2009 to 2011
$7.8M
Statistical Genetics and Genomics for Epidemiologic ResearchR01CA222833 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI SUN, WEI · 2018 to 2022
$2.2M
Methods for Analyzing Cancer Somatic Mutation DataR01CA223498 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HE, QIANCHUAN · 2018 to 2022
$2.0M
Post GWA Analysis of Inflammation Pathways in Barrett's and Esophageal CancerR21DK099804 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI MADELEINE, MARGARET M · 2014 to 2015
$484k
NCI NIH HHS P30 CA016056NCI NIH HHS R01 CA136725NCI NIH HHS R01 CA222833NCI NIH HHS R01 CA223498NIDDK NIH HHS R21 DK099804
6 · The paper itself

Abstract

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.

Indexed as

AdenocarcinomaAgedBarrett EsophagusBiomarkers, TumorCarrier ProteinsEsophageal NeoplasmsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGerm-Line MutationHumansMaleMiddle AgedPolymorphism, Single NucleotideReceptor, IGF Type 1Risk FactorsBiomarkers, TumorCarrier ProteinsIGF1R protein, humanReceptor, IGF Type 1Somatomedinssomatotropin-binding protein

Identifiers

PMID33300568
PMCPMC8052954
OpenAlexW3111482730

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.