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Adult height is associated with increased risk of ovarian cancer: A Mendelian randomisation study

  • Suzanne C. Dixon-Suen
  • , Christina M. Nagle
  • , Aaron P. Thrift
  • , Paul D.P. Pharoah
  • , Ailith Ewing
  • , Celeste Leigh Pearce
  • , Wei Zheng
  • , Georgia Chenevix-Trench
  • , Peter A. Fasching
  • , Matthias W. Beckmann
  • , Diether Lambrechts
  • , Ignace Vergote
  • , Sandrina Lambrechts
  • , Els Van Nieuwenhuysen
  • , Mary Anne Rossing
  • , Jennifer A. Doherty
  • , Kristine G. Wicklund
  • , Jenny Chang-Claude
  • , Audrey Y. Jung
  • , Kirsten B. Moysich
  • Kunle Odunsi, Marc T. Goodman, Lynne R. Wilkens, Pamela J. Thompson, Yurii B. Shvetsov, Thilo Dörk, Tjoung Won Park-Simon, Peter Hillemanns, Natalia Bogdanova, Ralf Butzow, Heli Nevanlinna, Liisa M. Pelttari, Arto Leminen, Francesmary Modugno, Roberta B. Ness, Robert P. Edwards, Joseph L. Kelley, Florian Heitz, Andreas Du Bois, Philipp Harter, Ira Schwaab, Beth Y. Karlan, Jenny Lester, Sandra Orsulic, Bobbie J. Rimel, Susanne K. Kjær, Estrid Høgdall, Allan Jensen, Ellen L. Goode, Brooke L. Fridley, Julie M. Cunningham, Stacey J. Winham, Graham G. Giles, Fiona Bruinsma, Roger L. Milne, Melissa C. Southey, Michelle A.T. Hildebrandt, Xifeng Wu, Karen H. Lu, Dong Liang, Douglas A. Levine, Maria Bisogna, Joellen M. Schildkraut, Andrew Berchuck, Daniel W. Cramer, Kathryn L. Terry, Elisa V. Bandera, Sara H. Olson, Helga B. Salvesen, Liv Cecilie Vestrheim Thomsen, Reidun K. Kopperud, Line Bjorge, Lambertus A. Kiemeney, Leon F.A.G. Massuger, Tanja Pejovic, Amanda Bruegl, Linda S. Cook, Nhu D. Le, Kenneth D. Swenerton, Angela Brooks-Wilson, Linda E. Kelemen, Jan Lubiński, Tomasz Huzarski, Jacek Gronwald, Janusz Menkiszak, Nicolas Wentzensen, Louise Brinton, Hannah Yang, Jolanta Lissowska, Claus K. Høgdall, Lene Lundvall, Honglin Song, Jonathan P. Tyrer, Ian Campbell, Diana Eccles, James Paul, Rosalind Glasspool, Nadeem Siddiqui, Alice S. Whittemore, Weiva Sieh, Valerie McGuire, Joseph H. Rothstein, Steven A. Narod, Catherine Phelan, Harvey A. Risch, John R. McLaughlin, Hoda Anton-Culver, Argyrios Ziogas, Usha Menon, Simon A. Gayther, Susan J. Ramus, Aleksandra Gentry-Maharaj, Anna H. Wu, Malcolm C. Pike, Chiu Chen Tseng, Jolanta Kupryjanczyk, Agnieszka Dansonka-Mieszkowska, Agnieszka Budzilowska, Iwona K. Rzepecka, Penelope M. Webb
  • Queensland Institute of Medical Research
  • University of Queensland
  • Baylor College of Medicine
  • University of Cambridge
  • University of Michigan, Ann Arbor
  • University of Southern California
  • Vanderbilt University
  • University of California at Los Angeles
  • Friedrich-Alexander University Erlangen-Nürnberg
  • Flanders Institute for Biotechnology
  • KU Leuven
  • Fred Hutchinson Cancer Research Center
  • University of Washington
  • Dartmouth College
  • German Cancer Research Center
  • University of Hamburg
  • Roswell Park Cancer Institute
  • Cedars-Sinai Medical Center
  • University of Hawai'i at Mānoa
  • Hannover Medical School
  • University of Helsinki
  • University of Pittsburgh
  • University of Texas Health Science Center at Houston
  • Kliniken Essen-Mitte
  • Dr. Horst Schmidt Klinik GmbH
  • Praxis für Humangenetik
  • Danish Cancer Society
  • University of Copenhagen
  • Mayo Clinic Rochester, MN
  • Moffitt Cancer Center
  • Cancer Council Victoria
  • University of Melbourne
  • Monash University
  • University of Texas MD Anderson Cancer Center
  • Texas Southern University
  • New York University
  • Memorial Sloan-Kettering Cancer Center
  • University of Virginia
  • Duke University
  • Brigham and Women’s Hospital
  • Harvard University
  • Rutgers - The State University of New Jersey, New Brunswick
  • University of Bergen
  • Radboud University Nijmegen
  • Oregon Health and Science University
  • University of New Mexico
  • Provincial Health Services Authority
  • University of British Columbia
  • Simon Fraser University
  • Medical University of South Carolina
  • Pomeranian Medical University in Szczecin
  • National Institutes of Health
  • Maria Sklodowska-Curie Institute of Oncology
  • Peter Maccallum Cancer Centre
  • University Hospital Southampton NHS Foundation Trust
  • University of Glasgow
  • Beatson Oncology Centre
  • NHS Greater Glasgow and Clyde
  • Stanford University
  • Icahn School of Medicine at Mount Sinai
  • University of Toronto
  • Yale University
  • Public Health Ontario
  • University of California at Irvine
  • University College London
  • Samuel Oschin Comprehensive Cancer Institute
  • University of New South Wales
  • Garvan Institute of Medical Research

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Background: Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias. Methods: We pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis. Results: Greater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours. Conclusions: Women with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis.

Original languageEnglish
Pages (from-to)1123-1129
Number of pages7
JournalBritish Journal of Cancer
Volume118
Issue number8
DOIs
StatePublished - Apr 1 2018

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