Evidence map›Paper›PMID 31211375›Full record

ArticleInternational journal of epidemiology2019

Association between genetically predicted polycystic ovary syndrome and ovarian cancer: a Mendelian randomization study.

Holly R Harris, Kara L Cushing-Haugen, Penelope M Webb, Christina M Nagle, Susan J Jordan, Australian Ovarian Cancer Study Group, Harvey A Risch, Mary Anne Rossing, Jennifer A Doherty, Marc T Goodman and 21 more

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

Article in International journal of epidemiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
4.6field-weighted citation impact, top 6% 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

24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.

  1. Pooled it
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  4. Review
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  8. Article
  9. Global epidemiology of epithelial ovarian cancer.Nature reviews. Clinical oncology · 2024
    Review
  10. Polycystic ovary syndrome.Nature reviews. Disease primers · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 17 institutions in 4 countries.

Holly R HarrisProgram in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Kara L Cushing-HaugenProgram in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Penelope M WebbPopulation Health Department, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Christina M NaglePopulation Health Department, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Susan J JordanPopulation Health Department, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Australian Ovarian Cancer Study Group
Harvey A RischDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
Mary Anne RossingProgram in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Jennifer A DohertyDepartment of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Marc T GoodmanCaner Prevention and Genetics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Francesmary ModugnoDivision of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Roberta B NessThe University of Texas School of Public Health, Houston, TX, USA.
Kirsten B MoysichDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
Susanne K KjærDepartment of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
Estrid HøgdallDepartment of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
Allan JensenDepartment of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
Joellen M SchildkrautDepartment of Public Health Sciences, The University of Virginia, Charlottesville, VA, USA.
Andrew BerchuckDepartment of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
Daniel W CramerObstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Elisa V BanderaDivision of Obstetrics and Gynecology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Lorna RodriguezDivision of Obstetrics and Gynecology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Nicolas WentzensenDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Joanne KotsopoulosEpidemiology Division, Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada.
Steven A NarodEpidemiology Division, Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada.
John R McLaughlinPublic Health Ontario, Samuel Lunenfeld Research Institute, Toronto, Canada.
Hoda Anton-CulverDepartment of Medicine, University of California Irvine, Irvine, CA, USA.
Argyrios ZiogasDepartment of Medicine, University of California Irvine, Irvine, CA, USA.
Celeste L PearceDepartment of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Anna H WuDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Sara LindströmProgram in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Kathryn L TerryObstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Brigham and Women's Hospital · USThe University of Queensland · AUUniversity of Copenhagen · DKUniversity of Southern California · USUniversity of Washington · USCedars-Sinai Medical Center · USUniversity of California, Irvine · USUniversity of Toronto · CADanish Cancer Society · DKDuke Medical Center · USFred Hutch Cancer Center · USLunenfeld-Tanenbaum Research Institute · CANational Cancer Institute · USRoswell Park Comprehensive Cancer Center · USRutgers Cancer Institute · USUniversity of Pittsburgh · USYale University · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CARYN LERMAN · 1985 to 2026
$181.4M
TRANSCRIPTIONAL PROFILINGP30CA072720 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI Tracie Saunders · 1997 to 2026
$94.5M
RPCI-UPCI Ovarian Cancer SPOREP50CA159981 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MOYSICH, KIRSTEN B., ODUNSI, KUNLE · 2013 to 2025
$19.6M
Novel Serum, Plasma, and Urine Biomarkers of Ovarian CanP50CA105009 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI CRAMER, DANIEL WILLIAM · 2004 to 2010
$13.3M
The Molecular Epidemiology Of Ovarian CancerR01CA076016 · NCI · DUKE UNIVERSITY · PI SCHILDKRAUT, JOELLEN M. · 1998 to 2010
$6.2M
OVARIAN CANCER RISK AND HYPERGONADOTROPIC HYPOGONADISMR01CA054419 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI CRAMER, DANIEL WILLIAM · 1992 to 2007
$5.9M
COLLABORATIVE STUDY OF OVARIAN CANCER IN TWO RISK GROUPSR01CA058598 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI GOODMAN, MARC T · 1993 to 2012
$4.6M
Epidemiology of Ovarian Cancer:New HypothesesR01CA087538 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ROSSING, MARY ANNE · 2002 to 2006
$3.5M
Steroid Hormone Genes and Ovarian Cancer RiskR01CA112523 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ROSSING, MARY ANNE · 2006 to 2010
$3.3M
The Mitochondrial Genome and Ovarian Cancer RiskR01CA149429 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI PHELAN, CATHERINE · 2010 to 2015
$3.1M
HEREDITARY BREAST CANCER--GENETIC AND MOLECULAR STUDIESR01CA058860 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI ANTON-CULVER, HODA A · 1994 to 2008
$3.1M
Interpretable Machine Learning to Identify Alzheimer's Disease Therapeutic TargetsR01AG061132 · NIA · UNIVERSITY OF WASHINGTON · PI LEE, SU-IN · 2019 to 2023
$2.9M
NCI NIH HHS K07 CA080668NCI NIH HHS K07 CA095666NCI NIH HHS K22 CA138563NCI NIH HHS K22 CA193860NCI NIH HHS N01 CN025403NCI NIH HHS P30 CA014089NCI NIH HHS P30 CA072720NCI NIH HHS P50 CA105009NCI NIH HHS P50 CA159981NCI NIH HHS R01 CA054419NCI NIH HHS R01 CA058598NCI NIH HHS R01 CA058860NCI NIH HHS R01 CA063678NCI NIH HHS R01 CA063682NCI NIH HHS R01 CA074850NCI NIH HHS R01 CA076016NCI NIH HHS R01 CA080742NCI NIH HHS R01 CA083918NCI NIH HHS R01 CA087538NCI NIH HHS R01 CA095023NCI NIH HHS R01 CA112523NCI NIH HHS R01 CA149429NCI NIH HHS R03 CA113148NCI NIH HHS R03 CA115195NIA NIH HHS R01 AG061132
6 · The paper itself

Abstract

backgroundPolycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4-21% in reproductive aged women. Recently, the Ovarian Cancer Association Consortium (OCAC) reported a decreased risk of invasive ovarian cancer among women with self-reported PCOS. However, given the limitations of self-reported PCOS, the validity of these observed associations remains uncertain. Therefore, we sought to use Mendelian randomization with genetic markers as a proxy for PCOS, to examine the association between PCOS and ovarian cancer.

methodsUtilizing 14 single nucleotide polymorphisms (SNPs) previously associated with PCOS we assessed the association between genetically predicted PCOS and ovarian cancer risk, overall and by histotype, using summary statistics from a previously conducted genome-wide association study (GWAS) of ovarian cancer among European ancestry women within the OCAC (22 406 with invasive disease, 3103 with borderline disease and 40 941 controls).

resultsAn inverse association was observed between genetically predicted PCOS and invasive ovarian cancer risk: odds ratio (OR)=0.92 [95% confidence interval (CI)=0.85-0.99; P = 0.03]. When results were examined by histotype, the strongest inverse association was observed between genetically predicted PCOS and endometrioid tumors (OR = 0.77; 95% CI = 0.65-0.92; P = 0.003). Adjustment for individual-level body mass index, oral contraceptive use and parity did not materially change the associations.

conclusionOur study provides evidence for a relationship between PCOS and reduced ovarian cancer risk, overall and among specific histotypes of invasive ovarian cancer. These results lend support to our previous observational study results. Future studies are needed to understand mechanisms underlying this association.

Indexed as

Adenocarcinoma, Clear CellAdenocarcinoma, MucinousCarcinoma, EndometrioidFemaleHumansMendelian Randomization AnalysisNeoplasms, Cystic, Mucinous, and SerousOvarian NeoplasmsPolycystic Ovary SyndromehistotypeMendelian randomizationovarian cancerPolycystic ovary syndrome

Identifiers

PMID31211375
PMCPMC6659359
OpenAlexW2951611776

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.