Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Lu Y, Cuellar-Partida G, Painter JN, Nyholt DR, Morris AP, Fasching PA, Hein A, Burghaus S, Beckmann M, Lambrechts D, Van Nieuwenhuysen E, Vergote I, Vanderstichele A, Doherty JA, Rossing MA, Wicklund KG, Chang-Claude J, Eilber U, Rudolph A, Wang-Gohrke S, Goodman MT, Bogdanova N, Doerk T, Duerst M, Hillemanns P, Runnebaum IB, Antonenkova N, Butzow R, Leminen A, Nevanlinna H, Pelttari LM, Edwards RP, Kelley JL, Modugno F, Moysich KB, Ness RB, Cannioto R, Hogdall E, Jensen A, Giles GG, Bruinsma F, Kjaer SK, Hildebrandt MAT, Liang D, Lu KH, Wu X, Bisogna M, Dao F, Levine DA, Cramer DW, Terry KL, Tworoger SS, Missmer S, Bjorge L, Salvesen HB, Kopperud RK, Bischof K, Aben KKH, Kiemeney LA, Massuger LFAG, Brooks-Wilson A, Olson SH, Mcguire V, Rothstein JH, Sieh W, Whittemore AS, Cook LS, Le ND, Gilks CB, Gronwald J, Jakubowska A, Lubinski J, Gawelko J, Song H, Tyrer JP, Wentzensen N, Brinton L, Trabert B, Lissowska J, Mclaughlin JR, Narod SA, Phelan C, Anton-Culver H, Ziogas A, Eccles D, Gayther SA, Gentry-Maharaj A, Menon U, Ramus SJ, Wu AH, Dansonka-Mieszkowska A, Kupryjanczyk J, Timorek A, Szafron L, Cunningham JM, Fridley BL, Winham SJ, Bandera EV, Poole EM, Morgan TK, Risch HA, Goode EL, Schildkraut JM, Webb PM, Pearce CL, Berchuck A, Pharoah PDP, Montgomery GW, Zondervan KT, Chenevix-Trench G, Macgregor S (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 24

Pages Range: 5955-64

Journal Issue: 20

DOI: 10.1093/hmg/ddv306

Abstract

Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.

Authors with CRIS profile

Involved external institutions

N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology Belarus (BY) Stanford University United States (USA) (US) Oregon Health and Science University (OSHU) United States (USA) (US) Harvard University United States (USA) (US) Rutgers Cancer Institute of New Jersey United States (USA) (US) Mayo Clinic United States (USA) (US) University of Kansas (KU) United States (USA) (US) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu Poland (PL) University of Southern California (USC) United States (USA) (US) University College London (UCL) United Kingdom (GB) University of Southampton United Kingdom (GB) University of California Irvine United States (USA) (US) H. Lee Moffitt Cancer Center & Research Institute United States (USA) (US) University of Toronto Canada (CA) Public Health Ontario Canada (CA) National Cancer Institute (NCI) United States (USA) (US) University of Cambridge United Kingdom (GB) Uniwersytet Rzeszowski Poland (PL) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) University of British Columbia Canada (CA) British Columbia Cancer Agency Canada (CA) University of New Mexico (UNM) / Universidad de Nuevo México United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Radboud University Nijmegen Netherlands (NL) Haukeland University Hospital / Haukeland universitetssykehus Norway (NO) Brigham and Women's Hospital (BWH) United States (USA) (US) University of Texas MD Anderson Cancer Center United States (USA) (US) Texas Southern University (TSU) United States (USA) (US) Danish Cancer Society Research Center Denmark (DK) Cancer Council Victoria Australia (AU) Monash University Australia (AU) Roswell Park Cancer Institute United States (USA) (US) University of Pittsburgh United States (USA) (US) Helsingin yliopisto / University of Helsinki Finland (FI) Friedrich-Schiller-Universität Jena Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Cedars-Sinai Medical Center United States (USA) (US) Universität Ulm Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Fred Hutchinson Cancer Research Center Canada (CA) University of Washington United States (USA) (US) Dartmouth College United States (USA) (US) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) University of California Los Angeles (UCLA) United States (USA) (US) University of Oxford United Kingdom (GB) Queensland University of Technology (QUT) Australia (AU) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Duke University United States (USA) (US) Yale University United States (USA) (US)

How to cite

APA:

Lu, Y., Cuellar-Partida, G., Painter, J.N., Nyholt, D.R., Morris, A.P., Fasching, P.A.,... Macgregor, S. (2015). Shared genetics underlying epidemiological association between endometriosis and ovarian cancer. Human Molecular Genetics, 24(20), 5955-64. https://doi.org/10.1093/hmg/ddv306

MLA:

Lu, Yi, et al. "Shared genetics underlying epidemiological association between endometriosis and ovarian cancer." Human Molecular Genetics 24.20 (2015): 5955-64.

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