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

Elisa V Bandera; Holly R Harris; Kara L Cushing-Haugen; John R McLaughlin; Penelope M Webb; Christina M Nagle; Susan J Jordan; Harvey A Risch; Mary Anne Rossing; Jennifer A Doherty; Marc T Goodman; Francesmary Modugno; Roberta B Ness; Kirsten B Moysich; Susanne K Kjær; Estrid Høgdall; Allan Jensen; Joellen M Schildkraut; Andrew Berchuck; Daniel W Cramer; Lorna Rodriguez; Nicolas Wentzensen; Joanne Kotsopoulos; Steven A Narod; Hoda Anton-Culver; Argyrios Ziogas; Celeste L Pearce; Anna H Wu; Sara Lindström; Kathryn L Terry; Australian Ovarian Cancer Study Group

doi:10.1093/ije/dyz113

Back

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

Journal article

Open access

Peer reviewed

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

Elisa V Bandera, Holly R Harris, Kara L Cushing-Haugen, John R McLaughlin, Penelope M Webb, Christina M Nagle, Susan J Jordan, Harvey A Risch, Mary Anne Rossing, Jennifer A Doherty, …

International journal of epidemiology, Vol.48(3), pp.822-830

06/01/2019

DOI: https://doi.org/10.1093/ije/dyz113

PMID: 31211375

Abstract

Adenocarcinoma, Clear Cell - epidemiology

Adenocarcinoma, Mucinous - epidemiology

Carcinoma, Endometrioid - epidemiology

Female

Humans

Mendelian Randomization Analysis

Neoplasms, Cystic, Mucinous, and Serous - epidemiology

Ovarian Neoplasms - epidemiology

Polycystic Ovary Syndrome - epidemiology

Polycystic Ovary Syndrome - genetics

Polycystic 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. Utilizing 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). An 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. Our 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.

Files and links (1)

url

https://doi.org/10.1093/ije/dyz113View

Version of Record (VoR) Open

Metrics

13 Record Views

22 Times Cited - Web of Science

See more details

Details

Title: Association between genetically predicted polycystic ovary syndrome and ovarian cancer: a Mendelian randomization study
Creators: Elisa V Bandera - Division of Obstetrics and Gynecology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA
Holly R Harris - Department of Epidemiology, University of Washington, Seattle, WA, USA
Kara L Cushing-Haugen - Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
John R McLaughlin - Public Health Ontario, Samuel Lunenfeld Research Institute, Toronto, Canada
Penelope M Webb - School of Public Health, University of Queensland, Herston, Queensland, Australia
Christina M Nagle - School of Public Health, University of Queensland, Herston, Queensland, Australia
Susan J Jordan - School of Public Health, University of Queensland, Herston, Queensland, Australia
Harvey A Risch - Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA
Mary Anne Rossing - Department of Epidemiology, University of Washington, Seattle, WA, USA
Jennifer A Doherty - Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
Marc T Goodman - Department of Biomedical Sciences, Community and Population Health Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Francesmary Modugno - Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Roberta B Ness - The University of Texas School of Public Health, Houston, TX, USA
Kirsten B Moysich - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
Susanne K Kjær - Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Estrid Høgdall - Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Allan Jensen - Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
Joellen M Schildkraut - Department of Public Health Sciences, The University of Virginia, Charlottesville, VA, USA
Andrew Berchuck - Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA
Daniel W Cramer - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Lorna Rodriguez - Division of Obstetrics and Gynecology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA
Nicolas Wentzensen - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Joanne Kotsopoulos - Epidemiology Division, Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada
Steven A Narod - Epidemiology Division, Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada
Hoda Anton-Culver - Department of Medicine, University of California Irvine, Irvine, CA, USA
Argyrios Ziogas - Department of Medicine, University of California Irvine, Irvine, CA, USA
Celeste L Pearce - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Anna H Wu - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Sara Lindström - Department of Epidemiology, University of Washington, Seattle, WA, USA
Kathryn L Terry - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Australian Ovarian Cancer Study Group
Publication Details: International journal of epidemiology, Vol.48(3), pp.822-830
Date published: 06/01/2019
Grant note: R03 CA113148 / NCI NIH HHS N01 CN025403 / NCI NIH HHS R01 CA058860 / NCI NIH HHS K22 CA193860 / NCI NIH HHS K22 CA138563 / NCI NIH HHS R01 CA063678 / NCI NIH HHS R03 CA115195 / NCI NIH HHS K07 CA095666 / NCI NIH HHS R01 CA112523 / NCI NIH HHS R01 CA149429 / NCI NIH HHS R01 CA063682 / NCI NIH HHS R01 CA058598 / NCI NIH HHS P50 CA159981 / NCI NIH HHS R01 CA080742 / NCI NIH HHS R01 AG061132 / NIA NIH HHS P50 CA105009 / NCI NIH HHS R01 CA083918 / NCI NIH HHS R01 CA074850 / NCI NIH HHS R01 CA054419 / NCI NIH HHS R01 CA095023 / NCI NIH HHS K07 CA080668 / NCI NIH HHS R01 CA076016 / NCI NIH HHS R01 CA087538 / NCI NIH HHS P30 CA014089 / NCI NIH HHS P30 CA072720 / NCI NIH HHS
Academic Unit: Cancer Epidemiology and Health Outcomes
Language: English
Resource Type: Journal article
Identifiers: 991031665507004646