Evidence map›Paper›PMID 30541042›Full record

SynthesisJournal of the National Cancer Institute2019

Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer.

Naomi Walsh, Han Zhang, Paula L Hyland, Qi Yang, Evelina Mocci, Mingfeng Zhang, Erica J Childs, Irene Collins, Zhaoming Wang, Alan A Arslan and 94 more

Open access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Journal of the National Cancer Institute, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 22% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pathway Analysis of Renal Cell Carcinoma Genome-Wide Association Studies Identifies Novel Associations.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020
    Pooled it
  2. Article
  3. Article
  4. Article
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  6. Pancreatic Adenocarcinoma: Trends in Epidemiology, Risk Factors, and Outcomes.Hematology/oncology clinics of North America · 2022
    Review
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  17. Associations of novel variants inAmerican journal of cancer research · 2020
    Article
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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

104 authors at 20 institutions in 14 countries.

Naomi WalshNational Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin, Ireland.
Han ZhangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Paula L HylandDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Qi YangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Evelina MocciDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD.
Mingfeng ZhangLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Erica J ChildsDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD.
Irene CollinsLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Zhaoming WangLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Alan A ArslanDepartment of Obstetrics and Gynecology, New York University School of Medicine, New York, NY.
Laura Beane-FreemanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Paige M BracciDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA.
Paul BrennanInternational Agency for Research on Cancer (IARC), Lyon, France.
Federico CanzianGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Eric J DuellUnit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain.
Steven GallingerProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Graham G GilesCancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Michael GogginsDepartment of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD.
Gary E GoodmanDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
Phyllis J GoodmanSWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA.
Rayjean J HungProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
Robert C KurtzDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Núria MalatsGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Loic LeMarchandCancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI.
Rachel E NealePopulation Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Sara H OlsonDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
Ghislaine SceloInternational Agency for Research on Cancer (IARC), Lyon, France.
Xiao O ShuDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN.
Stephen K Van Den EedenDivision of Research, Kaiser Permanente Northern California, Oakland, CA.
Kala VisvanathanDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Emily WhiteDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN.
PanScan and PanC4 consortia
Demetrius AlbanesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Gabriella AndreottiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Ana BabicDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
William R BamletDepartment of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN.
Sonja I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Ayelet BorgidaProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Marie-Christine Boutron-RuaultCentre de Recherche en Épidémiologie et Santé des Populations (CESP, Inserm U1018), Facultés de Medicine, Université Paris-Saclay, UPS, UVSQ, Gustave Roussy, Villejuif, France.
Lauren BraisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Paul BrennanInternational Agency for Research on Cancer (IARC), Lyon, France.
Bas Bueno-de-MesquitaDepartment for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
Julie BuringDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA.
Kari G ChaffeeDepartment of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN.
Stephen ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Sean ClearyDivision of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN.
Michelle CotterchioCancer Care Ontario, University of Toronto, Toronto, ON, Canada.
Lenka ForetovaDepartment of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Charles FuchsYale Cancer Center, New Haven, CT.
J Michael M GazianoDivision of Aging, Brigham and Women's Hospital, Boston, MA.
Edward GiovannucciDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Michael GogginsDepartment of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD.
Thilo HackertDepartment of General Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Christopher HaimanDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Patricia HartgeDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Manal HasanDepartment of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX.
Kathy J HelzlsouerDivision of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Joseph HermanDepartment of Radiation Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD.
Ivana HolcatovaInstitute of Public Health and Preventive Medicine, Charles University, 2nd Faculty of Medicine, Prague, Czech Republic.
Elizabeth A HollyDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA.
Robert HooverDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Rayjean J HungProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Vladimir JanoutDepartment of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Czech Republic.
Eric A KleinGlickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH.
Robert C KurtzDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Daniel LaheruDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD.
I-Min LeeDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA.
Lingeng LuDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT.
Núria MalatsGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Satu MannistoDepartment of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.
Roger L MilneCancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Ann L ObergDepartment of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN.
Irene OrlowDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
Alpa V PatelEpidemiology Research Program, American Cancer Society, Atlanta, GA.
Ulrike PetersDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
Miquel PortaCIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
Francisco X RealCIBERONC, Madrid, Spain.
Nathaniel RothmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Howard D SessoDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA.
Gianluca SeveriCancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Debra SilvermanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Oliver StrobelDepartment of General Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Malin SundDepartment of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
Mark D ThornquistDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
Geoffrey S TobiasDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Jean Wactawski-WendeDepartment of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY.
Nick WarehamMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Elisabete WeiderpassDepartment of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
Nicolas WentzensenDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
William WheelerInformation Management Systems, Silver Spring, MD.
Herbert YuPerlmutter Cancer Center, New York University School of Medicine, New York, NY.
Anne Zeleniuch-JacquotteDepartment of Population Health, New York University School of Medicine, New York, NY.
Peter KraftDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
Donghui LiDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.
Eric J JacobsEpidemiology Research Program, American Cancer Society, Atlanta, GA.
Gloria M PetersenDepartment of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN.
Brian M WolpinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Harvey A RischDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT.
Laufey T AmundadottirLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Kai YuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Alison P KleinDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD.
Rachael Z Stolzenberg-SolomonNational Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin, Ireland.
National Institutes of Health · USBrigham and Women's Hospital · USJohns Hopkins University · USAmerican Cancer Society · USFred Hutch Cancer Center · USMayo Clinic · USMemorial Sloan Kettering Cancer Center · USCentre international de recherche sur le cancer · FRCleveland Clinic · USDublin City University · IEInserm · FRLunenfeld-Tanenbaum Research Institute · CAThe University of Melbourne · AUThe University of Texas MD Anderson Cancer Center · USUniversitat Autònoma de Barcelona · ESUniversity of California, San Francisco · USUniversity of Southern California · USUniversity of Toronto · CAVanderbilt University · USYale University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
SWOG Foreign AccrualsU10CA037429 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI BLANKE, CHARLES D., MEYSKENS, FRANK L. · 1985 to 2014
$205.2M
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
SWOG NCORP Research BaseUG1CA189974 · NCI · THE HOPE FOUNDATION · PI CHARLES D. BLANKE, DAWN HERSHMAN · 2014 to 2026
$80.6M
Tumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI THOMPSON, ELIZABETH D · 1993 to 2022
$54.6M
Understanding Population Differences in Cancer: The MEC StudyU01CA164973 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI HAIMAN, CHRISTOPHER ALAN, LE MARCHAND, LOIC · 2015 to 2025
$37.4M
Data sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8M
THE CAROTENE AND RETINOL EFFICACY TRIAL (CARET)U01CA063673 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GOODMAN, GARY E · 1994 to 2006
$13.0M
ONTARIO REGISTRY FOR STUDIES OF FAMILIAL COLON CANCERU01CA074783 · NCI · CANCER CARE ONTARIO · PI GALLINGER, STEVEN · 1997 to 2008
$12.5M
Whole Genome Scan in the Pancreatic Cancer Cohort Consortium (PanScan)ZIACP010193 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI STOLZENBERG-SOLOMON, RACHAEL · 2009 to 2025
$9.5M
Validation and Fine-Scale Mapping of Pancreatic Cancer Susceptibility Loci (Study)R01CA154823 · NCI · JOHNS HOPKINS UNIVERSITY · PI KLEIN, ALISON P · 2011 to 2020
$5.7M
PCPT and SELECT Cohorts: Core Infrastructure Support for Cancer ResearchU01CA182883 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI TANGEN, CATHERINE M., THOMPSON, IAN M. · 2019 to 2023
$5.4M
CCR NIH HHS HHSN261200800001CMedical Research Council MC_UU_12015/1NCATS NIH HHS UL1 TR001863NCI NIH HHS HHSN261200800001ENCI NIH HHS K07 CA222159NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA062924NCI NIH HHS R01 CA154823NCI NIH HHS U01 CA063673NCI NIH HHS U01 CA074783NCI NIH HHS U01 CA164973NCI NIH HHS U01 CA167462NCI NIH HHS U01 CA167551NCI NIH HHS U01 CA182883NCI NIH HHS U10 CA037429NCI NIH HHS UG1 CA189974NCI NIH HHS UM1 CA167462NCI NIH HHS UM1 CA182883NCI NIH HHS UM1 CA182934World Health Organization 001
6 · The paper itself

Abstract

backgroundGenome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes.

methodsWe conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided.

resultsWe identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets.

conclusionOur agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.

Indexed as

Carcinoma, Pancreatic DuctalCase-Control StudiesGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansModels, StatisticalPancreatic NeoplasmsPolymorphism, Single Nucleotide

Identifiers

PMID30541042
PMCPMC6579744
OpenAlexW2905221341

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