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

Dixon-Suen SC, Nagle CM, Thrift AP, Pharoah PDP, Ewing A, Pearce CL, Zheng W, Chenevix-Trench G, Fasching P, Beckmann M, Lambrechts D, Vergote I, Lambrechts S, Van Nieuwenhuysen E, Rossing MA, Doherty JA, Wicklund KG, Chang-Claude J, Jung AY, Moysich KB, Odunsi K, Goodman MT, Wilkens LR, Thompson PJ, Shvetsov YB, Doerk T, Park-Simon TW, Hillemanns P, Bogdanova N, Butzow R, Nevanlinna H, Pelttari LM, Leminen A, Modugno F, Ness RB, Edwards RP, Kelley JL, Heitz F, Du Bois A, Harter P, Schwaab I, Karlan BY, Lester J, Orsulic S, Rimel BJ, Kjaer SK, Hogdall E, Jensen A, Goode EL, Fridley BL, Cunningham JM, Winham SJ, Giles GG, Bruinsma F, Milne RL, Southey MC, Hildebrandt MAT, Wu X, Lu KH, Liang D, Levine DA, Bisogna M, Schildkraut JM, Berchuck A, Cramer DW, Terry KL, Bandera EV, Olson SH, Salvesen HB, Thomsen LCV, Kopperud RK, Bjorge L, Kiemeney LA, Massuger LFAG, Pejovic T, Bruegl A, Cook LS, Le ND, Swenerton KD, Brooks-Wilson A, Kelemen LE, Lubinski J, Huzarski T, Gronwald J, Menkiszak J, Wentzensen N, Brinton L, Yang H, Lissowska J, Hogdall CK, Lundvall L, Song H, Tyrer JP, Campbell I, Eccles D, Paul J, Glasspool R, Siddiqui N, Whittemore AS, Sieh W, Mcguire V, Rothstein JH, Narod SA, Phelan C, Risch HA, Mclaughlin JR, Anton-Culver H, Ziogas A, Menon U, Gayther SA, Ramus SJ, Gentry-Maharaj A, Wu AH, Pike MC, Tseng CC, Kupryjanczyk J, Dansonka-Mieszkowska A, Budzilowska A, Rzepecka IK, Webb PM (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 118

Pages Range: 1123-1129

Journal Issue: 8

DOI: 10.1038/s41416-018-0011-3

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.

Authors with CRIS profile

Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Vanderbilt University United States (USA) (US) University of Michigan United States (USA) (US) Kliniken Essen-Mitte Germany (DE) University of Hawaii (U.H.) United States (USA) (US) Cedars-Sinai Medical Center United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS) Finland (FI) Houston Texas Medical Center United States (USA) (US) Helsingin yliopisto / University of Helsinki Finland (FI) University of Pittsburgh United States (USA) (US) University of Cambridge United Kingdom (GB) Dartmouth College United States (USA) (US) Fred Hutchinson Cancer Research Center United States (USA) (US) Roswell Park Cancer Institute United States (USA) (US) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Icahn School of Medicine at Mount Sinai United States (USA) (US) Public Health Ontario Canada (CA) University of Southampton United Kingdom (GB) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) University of California Irvine United States (USA) (US) University of Copenhagen Denmark (DK) Samuel Oschin Comprehensive Cancer Institute United States (USA) (US) University of Toronto Canada (CA) Yale University United States (USA) (US) Stanford University United States (USA) (US) University College London (UCL) United Kingdom (GB) University of Glasgow United Kingdom (GB) University of Southern California (USC) United States (USA) (US) H. Lee Moffitt Cancer Center & Research Institute United States (USA) (US) University of New South Wales (UNSW) Australia (AU) Beatson West of Scotland Cancer Centre (BWSCC) United Kingdom (GB) Radboud University Nijmegen Netherlands (NL) Danish Cancer Society Research Center Denmark (DK) University of New Mexico (UNM) / Universidad de Nuevo México United States (USA) (US) Medical University of South Carolina (MUSC) United States (USA) (US) Oregon Health and Science University (OSHU) United States (USA) (US) National Cancer Institute (NCI) United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Brigham and Women's Hospital (BWH) United States (USA) (US) Duke University United States (USA) (US) University of Virginia (UVA) United States (USA) (US) Cancer Council Victoria Australia (AU) British Columbia Cancer Agency Canada (CA) New York University (NYU) United States (USA) (US) Mayo Clinic United States (USA) (US) Peter MacCallum Cancer Centre Australia (AU) Haukeland University Hospital / Haukeland universitetssykehus Norway (NO) University of Texas MD Anderson Cancer Center United States (USA) (US) University of British Columbia Canada (CA) The University of Melbourne Australia (AU) Rutgers Cancer Institute of New Jersey United States (USA) (US) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University of Texas Health Science Center at Houston (UTHealth) United States (USA) (US) Texas Southern University (TSU) United States (USA) (US) Glasgow Royal Infirmary (GRI) United Kingdom (GB)

How to cite

APA:

Dixon-Suen, S.C., Nagle, C.M., Thrift, A.P., Pharoah, P.D.P., Ewing, A., Pearce, C.L.,... Webb, P.M. (2018). Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study. British Journal of Cancer, 118(8), 1123-1129. https://doi.org/10.1038/s41416-018-0011-3

MLA:

Dixon-Suen, Suzanne C., et al. "Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study." British Journal of Cancer 118.8 (2018): 1123-1129.

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