Evidence map›Paper›PMID 36210504›Full record

ArticleJournal of the National Cancer Institute2022

Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci.

Amber A DeVries, Joe Dennis, Jonathan P Tyrer, Pei-Chen Peng, Simon G Coetzee, Alberto L Reyes, Jasmine T Plummer, Brian D Davis, Stephanie S Chen, Felipe Segato Dezem and 80 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.4field-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

9 citing papers in PubMed, 13 citations in OpenAlex.

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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

90 authors at 20 institutions in 14 countries.

Amber A DeVriesCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Joe DennisCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.ORCID 0000-0003-4591-1214
Jonathan P TyrerCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Pei-Chen PengCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Simon G CoetzeeCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Alberto L ReyesCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Jasmine T PlummerCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0001-7263-350X
Brian D DavisCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Stephanie S ChenCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Felipe Segato DezemCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Katja K H AbenRadboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Hoda Anton-CulverDepartment of Medicine, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA.ORCID 0000-0002-9603-0110
Natalia N AntonenkovaN.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
Matthias W BeckmannDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
Alicia Beeghly-FadielDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Andrew BerchuckDepartment of Gynecologic Oncology, Duke University Hospital, Durham, NC, USA.
Natalia V BogdanovaN.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
Nadja Bogdanova-MarkovInstitute of Human Genetics, University of Münster, Münster, Germany.
James D BrentonCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Ralf ButzowDepartment of Pathology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Ian CampbellCancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.ORCID 0000-0002-7773-4155
Jenny Chang-ClaudeDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Georgia Chenevix-TrenchDepartment of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID 0000-0002-1878-2587
Linda S CookEpidemiology, School of Public Health, University of Colorado, Aurora, CO, USA.
Anna DeFazioCentre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia.
Jennifer A DohertyHuntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
Thilo DörkGynaecology Research Unit, Hannover Medical School, Hannover, Germany.
Diana M EcclesFaculty of Medicine, University of Southampton, Southampton, UK.
A Heather EliassenChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-3961-6609
Peter A FaschingDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
Renée T FortnerDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Graham G GilesCancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Ellen L GoodeDepartment of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
Marc T GoodmanSamuel Oschin Comprehensive Cancer Institute, Cancer Prevention and Genetics Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Jacek GronwaldDepartment of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
OPAL Study Group
AOCS Group
Niclas HåkanssonInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Michelle A T HildebrandtDepartment of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Chad HuffDepartment of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
David G HuntsmanDepartment of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
Allan JensenDepartment of Lifestyle, Reproduction and Cancer, Danish Cancer Society Research Center, Copenhagen, Denmark.ORCID 0000-0001-8124-4880
Siddhartha KarMedical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.ORCID 0000-0002-2314-1426
Beth Y KarlanDavid Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, CA, USA.
Elza K KhusnutdinovaInstitute of Biochemistry and Genetics, Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia.
Lambertus A KiemeneyRadboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Susanne K KjaerDepartment of Lifestyle, Reproduction and Cancer, Danish Cancer Society Research Center, Copenhagen, Denmark.
Jolanta KupryjanczykDepartment of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Marilyne LabrieKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Diether LambrechtsVIB Center for Cancer Biology, VIB, Leuven, Belgium.
Nhu D LeCancer Control Research, BC Cancer, Vancouver, BC, Canada.
Jan LubińskiDepartment of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Taymaa MayDivision of Gynecologic Oncology, University Health Network, Princess Margaret Hospital, Toronto, Ontario, Canada.
Usha MenonMRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK.ORCID 0000-0003-3708-1732
Roger L MilneCancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Francesmary ModugnoWomen's Cancer Research Center, Magee-Womens Research Institute and Hillman Cancer Center, Pittsburgh, PA, USA.
Alvaro N MonteiroDepartment of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
Kirsten B MoysichDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
Kunle OdunsiDepartment of Oncology, University of Chicago Medicine Comprehensive Cancer Center, Chicago, IL, USA.
Håkan OlssonOncology, Department of Clinical Sciences, Lund University, Lund, Sweden.
Celeste L PearceDepartment of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Tanja PejovicLaboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.
Susan J RamusSchool of Women's and Children's Health, Faculty of Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.
Elio RiboliImperial College London, London, UK.ORCID 0000-0001-6795-6080
Marjorie J RigganDepartment of Gynecologic Oncology, Duke University Hospital, Durham, NC, USA.
Isabelle RomieuNutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
Dale P SandlerEpidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Joellen M SchildkrautDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
V Wendy SetiawanDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Weiva SiehDepartment of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-0085-1190
Honglin SongDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Rebecca SutphenEpidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA.
Kathryn L TerryDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Pamela J ThompsonSamuel Oschin Comprehensive Cancer Institute, Cancer Prevention and Genetics Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Linda TitusMuskie School of Public Policy, Public Health, Portland, ME, USA.
Shelley S TworogerDepartment of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
Els Van NieuwenhuysenDivision of Gynecologic Oncology, Department of Gynecology and Obstetrics, Leuven Cancer Institute, Leuven, Belgium.
Digna Velez EdwardsDivision of Quantitative Sciences, Department of Obstetrics and Gynecology, Department of Biomedical Sciences, Women's Health Research, Vanderbilt University Medical Center, Nashville, TN, USA.
Penelope M WebbPopulation Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID 0000-0003-0733-5930
Nicolas WentzensenDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID 0000-0003-1251-0836
Alice S WhittemoreDepartment of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA.
Alicja WolkInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-7387-6845
Anna H WuDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Argyrios ZiogasDepartment of Medicine, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA.ORCID 0000-0003-4529-3727
Matthew L FreedmanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Kate LawrensonDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Women's Cancer Program at the Samuel Oschin Cancer Institute Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0002-6469-2515
Paul D P PharoahCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Douglas F EastonCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Simon A GaytherCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Michelle R JonesCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0001-5466-3844
Cedars-Sinai Medical Center · USQIMR Berghofer Medical Research Institute · AUUniversity of Southern California · USDuke University Hospital · USThe University of Texas MD Anderson Cancer Center · USUniversity of Cambridge · GBOregon Health & Science University · USUppsala University · SEEmory University · USRadboud University Nijmegen · NLRoswell Park Comprehensive Cancer Center · USThe University of Melbourne · AUThe University of Sydney · AUBrigham and Women's Hospital · USPomeranian Medical University · PLUniversity Health Network · CAUniversity of British Columbia · CAUniversity of California, Los Angeles · USVIB-KU Leuven Center for Cancer Biology · BEDana-Farber Cancer Institute · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3M
Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ROSNER, BERNARD A · 2000 to 2019
$77.8M
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI ELLEN L. GOODE · 2009 to 2026
$37.0M
WITHIN SUBJ VARIABILITY IN MEASUREMENTS DRUG METABOL ENZYMES IN HLTY SUBJM01RR000056 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEVINE, ARTHUR S · 1985 to 2006
$29.2M
Life Course Cancer Epidemiology Cohort in WomenU01CA176726 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI ELIASSEN, A. HEATHER, WILLETT, WALTER C. · 2018 to 2025
$22.4M
Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3M
RPCI-UPCI Ovarian Cancer SPOREP50CA159981 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MOYSICH, KIRSTEN B., ODUNSI, KUNLE · 2013 to 2025
$19.6M
USC CANCER EPIDEMIOLOGY &BIOSTATISTICS UNITP01CA017054 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DEAPEN, DENNIS M. · 1985 to 2009
$18.2M
Life Course Cancer Epidemiology Cohort in WomenUM1CA176726 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI WILLETT, WALTER C. · 2013 to 2017
$15.7M
Novel Serum, Plasma, and Urine Biomarkers of Ovarian CanP50CA105009 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI CRAMER, DANIEL WILLIAM · 2004 to 2010
$13.3M
Breast Cancer NowCancer Research UK 14136Cancer Research UK C490/A10119 C490/A10124Cancer Research UK C570/A16491Cancer Research UK C8221/A19170Department of HealthIntramural NIH HHS Z01 ES044005Intramural NIH HHS Z01 ES049033Medical Research Council 1000143Medical Research Council G0401527Medical Research Council G1000143Medical Research Council MC_UU_00004/01Medical Research Council MR/M012190/1Medical Research Council MR/N003284/1Medical Research Council MR_UU_12023NCATS NIH HHS ULTR000445NCI NIH HHS K07 CA080668NCI NIH HHS K07-CA080668NCI NIH HHS N01 CN025403NCI NIH HHS N01 PC067010NCI NIH HHS P01 CA017054NCI NIH HHS P01 CA087969NCI NIH HHS P30 CA014089NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA047904NCI NIH HHS P50 CA105009NCI NIH HHS P50 CA136393NCI NIH HHS P50 CA159981NCI NIH HHS R01 CA049449NCI NIH HHS R01 CA054419NCI NIH HHS R01 CA058598NCI NIH HHS R01 CA058860NCI NIH HHS R01 CA067262NCI NIH HHS R01 CA076016NCI NIH HHS R01 CA095023NCI NIH HHS R01 CA106414NCI NIH HHS R01 CA122443NCI NIH HHS R01 CA126841NCI NIH HHS R01 CA149429NCI NIH HHS R01 CA160669NCI NIH HHS R01 CA248288NCI NIH HHS R01- CA61107NCI NIH HHS R03 CA113148NCI NIH HHS R03 CA115195NCI NIH HHS U01 CA176726NCI NIH HHS U19 CA148112NCI NIH HHS U19-CA148112NCI NIH HHS UM1 CA176726NCI NIH HHS UM1 CA186107NCRR NIH HHS M01 RR000056NCRR NIH HHS S10 RR025141NHGRI NIH HHSNIEHS NIH HHS Z01-ES044005NIGMS NIH HHS T32 GM118288NIH HHS 5T32GM118288-03NIH HHS CA1X01HG007491-01NIH HHS R01-CA058860NIH HHS R01-CA106414-A2NIH HHS R01-CA122443NIH HHS R01-CA54419NIH HHS R01-CA58598NIH HHS R01-CA76016Wellcome Trust 076113Wellcome Trust 209057World Health Organization 001Worldwide Cancer Research
6 · The paper itself

Abstract

backgroundKnown risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort.

methodsSingle nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types.

resultsWe identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P < .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P < .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types.

conclusionsCNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention.

Indexed as

Genome-Wide Association StudyOvarian NeoplasmsAllelesCarcinoma, Ovarian EpithelialDNA Copy Number VariationsFemaleGenetic Predisposition to DiseaseHumansPolymorphism, Single Nucleotide

Identifiers

PMID36210504
PMCPMC9949586
OpenAlexW4304118598

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