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

doi:10.1038/s41416-018-0011-3

Meta-Analysis

. 2018 Apr;118(8):1123-1129.

doi: 10.1038/s41416-018-0011-3. Epub 2018 Mar 20.

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

Suzanne C Dixon-Suen^{1

2}, Christina M Nagle^{3

4}, Aaron P Thrift⁵, Paul D P Pharoah⁶, Ailith Ewing⁶, Celeste Leigh Pearce^{7

8}, Wei Zheng⁹; Australian Ovarian Cancer Study Group; Georgia Chenevix-Trench¹⁰, Peter A Fasching^{11

12}, Matthias W Beckmann¹², Diether Lambrechts^{13

14}, Ignace Vergote¹⁵, Sandrina Lambrechts¹⁵, Els Van Nieuwenhuysen¹⁵, Mary Anne Rossing^{16

17}, Jennifer A Doherty¹⁸, Kristine G Wicklund¹⁶, Jenny Chang-Claude^{19

20}, Audrey Y Jung¹⁹, Kirsten B Moysich²¹, Kunle Odunsi²², Marc T Goodman^{23

24}, Lynne R Wilkens²⁵, Pamela J Thompson²³, Yurii B Shvetsov²⁵, Thilo Dörk²⁶, Tjoung-Won Park-Simon²⁶, Peter Hillemanns²⁶, Natalia Bogdanova²⁷, Ralf Butzow²⁸, Heli Nevanlinna²⁹, Liisa M Pelttari²⁹, Arto Leminen²⁹, Francesmary Modugno^{30

31

32}, Roberta B Ness³³, Robert P Edwards^{30

31}, Joseph L Kelley³⁰, Florian Heitz^{34

35}, Andreas du Bois^{34

35}, Philipp Harter^{34

35}, Ira Schwaab³⁶, Beth Y Karlan³⁷, Jenny Lester³⁷, Sandra Orsulic³⁷, Bobbie J Rimel³⁷, Susanne K Kjær^{38

39}, Estrid Høgdall^{38

40}, Allan Jensen³⁸, Ellen L Goode⁴¹, Brooke L Fridley⁴², Julie M Cunningham⁴³, Stacey J Winham⁴⁴, Graham G Giles^{45

46

47}, Fiona Bruinsma⁴⁵, Roger L Milne^{45

46}, Melissa C Southey⁴⁸, Michelle A T Hildebrandt⁴⁹, Xifeng Wu⁴⁹, Karen H Lu⁵⁰, Dong Liang⁵¹, Douglas A Levine⁵², Maria Bisogna⁵³, Joellen M Schildkraut⁵⁴, Andrew Berchuck⁵⁵, Daniel W Cramer⁵⁶, Kathryn L Terry^{56

57}, Elisa V Bandera^{58

59}, Sara H Olson⁶⁰, Helga B Salvesen^{61

62}, Liv Cecilie Vestrheim Thomsen^{61

62}, Reidun K Kopperud^{61

62}, Line Bjorge^{61

62}, Lambertus A Kiemeney⁶³, Leon F A G Massuger⁶⁴, Tanja Pejovic^{65

66}, Amanda Bruegl⁶⁵, Linda S Cook⁶⁷, Nhu D Le⁶⁸, Kenneth D Swenerton⁶⁹, Angela Brooks-Wilson^{70

71}, Linda E Kelemen⁷², Jan Lubiński⁷³, Tomasz Huzarski⁷³, Jacek Gronwald⁷³, Janusz Menkiszak⁷⁴, Nicolas Wentzensen⁷⁵, Louise Brinton⁷⁵, Hannah Yang⁷⁵, Jolanta Lissowska⁷⁶, Claus K Høgdall³⁹, Lene Lundvall³⁹, Honglin Song⁶, Jonathan P Tyrer⁶, Ian Campbell^{77

78}, Diana Eccles⁷⁹, James Paul⁸⁰, Rosalind Glasspool⁸¹, Nadeem Siddiqui⁸², Alice S Whittemore⁸³, Weiva Sieh⁸⁴, Valerie McGuire⁸³, Joseph H Rothstein⁸⁴, Steven A Narod⁸⁵, Catherine Phelan⁸⁶, Harvey A Risch⁸⁷, John R McLaughlin⁸⁸, Hoda Anton-Culver^{89

90}, Argyrios Ziogas⁸⁹, Usha Menon⁹¹, Simon A Gayther⁹², Susan J Ramus^{93

94}, Aleksandra Gentry-Maharaj⁹¹, Anna H Wu⁸, Malcolm C Pike^{8

60}, Chiu-Chen Tseng⁸, Jolanta Kupryjanczyk⁹⁵, Agnieszka Dansonka-Mieszkowska⁹⁵, Agnieszka Budzilowska⁹⁵, Iwona K Rzepecka⁹⁵, Penelope M Webb^{3

4}; Ovarian Cancer Association Consortium

Affiliations

¹ Gynaecological Cancers Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD 4006, Australia. Suzanne.Dixon@qimrberghofer.edu.au.
² The University of Queensland, School of Public Health, Level 2 Public Health Building (887), Corner of Herston Road & Wyndham Street, Brisbane, QLD 4006, Australia. Suzanne.Dixon@qimrberghofer.edu.au.
³ Gynaecological Cancers Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD 4006, Australia.
⁴ The University of Queensland, School of Public Health, Level 2 Public Health Building (887), Corner of Herston Road & Wyndham Street, Brisbane, QLD 4006, Australia.
⁵ Department of Medicine and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
⁶ Strangeways Research Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health & Primary Care/Department of Oncology, University of Cambridge, Worts Causeway, Cambridge, CB1 8RN, UK.
⁷ Department of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights, SPH Tower, Ann Arbor, MI, 48109-2029, USA.
⁸ Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA, 90033, USA.
⁹ Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, 2525 West End Ave., Nashville, TN, 37203, USA.
¹⁰ Cancer Genetics Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD 4006, Australia.
¹¹ Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA.
¹² Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Universitätsstrasse 21-23, 91054, Erlangen, Germany.
¹³ Vesalius Research Center, VIB, Herestraat 49, bus 912, 3000, Leuven, Belgium.
¹⁴ Laboratory for Translational Genetics, Department of Oncology, University of Leuven, O&N IV Herestraat 49-Box 912, 3000, Leuven, Belgium.
¹⁵ Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Herestraat 49, Leuven, 3000, Belgium.
¹⁶ Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA, 98109-1024, USA.
¹⁷ Department of Epidemiology, University of Washington, 1959 NE Pacific Street, Health Sciences Bldg, F-262, Seattle, WA, 98195, USA.
¹⁸ Department of Epidemiology, The Geisel School of Medicine at Dartmouth, 1 Medical Center Drive, 7927 Rubin Building, Lebanon, NH, 03756, USA.
¹⁹ Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 581, Heidelberg, 69120, Germany.
²⁰ University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
²¹ Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
²² Department of Gynecological Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
²³ Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA, 90048, USA.
²⁴ Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA, 90048, USA.
²⁵ Cancer Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA.
²⁶ Clinics of Obstetrics and Gynaecology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625, Hannover, Germany.
²⁷ Radiation Oncology Research Unit, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625, Hannover, Germany.
²⁸ Department of Pathology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 8, 00029, Helsinki, Finland.
²⁹ Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 8, 00029, Helsinki, Finland.
³⁰ Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, 300 Halket Street, Pittsburgh, PA, 15213, USA.
³¹ Ovarian Cancer Center of Excellence, Women's Cancer Research Program, Magee-Women's Research Institute and University of Pittsburgh Cancer Institute, 204 Craft Avenue, Pittsburgh, PA, 15213, USA.
³² Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, 130 De Soto Street, Pittsburgh, PA, 15261, USA.
³³ The University of Texas Health Science Center at Houston, School of Public Health, 1200 Herman Pressler, Suite E-1015, Houston, TX, 77030, USA.
³⁴ Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/ Evang. Huyssens-Stiftung/ Knappschaft GmbH, Henricistrasse 92, 45136, Essen, Germany.
³⁵ Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Ludwig-Erhard-Strasse 100, 65199, Wiesbaden, Germany.
³⁶ Praxis für Humangenetik, Biebricher Allee 117, 65187, Wiesbaden, Germany.
³⁷ Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8635 West Third Street, Los Angeles, CA, 90048, USA.
³⁸ Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100, Copenhagen, Denmark.
³⁹ Department of Gynaecology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
⁴⁰ Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2370, Herlev, Denmark.
⁴¹ Department of Health Science Research, Division of Epidemiology, Mayo Clinic, 200 First Street SW, Charlton 6, Rochester, MN, 55905, USA.
⁴² Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
⁴³ Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Stabile 13, Rochester, MN, 55905, USA.
⁴⁴ Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, 200 First Street SW, Charlton 6, Rochester, MN, 55905, USA.
⁴⁵ Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC 3004, Australia.
⁴⁶ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Grattan Street, Parkville, VIC 3010, Australia.
⁴⁷ Department of Epidemiology and Preventive Medicine, Monash University, The Alfred Centre, 99 Commercial Road, Melbourne, VIC 3004, Australia.
⁴⁸ Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Grattan Street, Carlton, VIC 3053, Australia.
⁴⁹ Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1155 Pressler Blvd-Unit 1340, Houston, TX, 77030, USA.
⁵⁰ Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1155 Pressler Blvd - Unit 1340, Houston, TX, 77030, USA.
⁵¹ College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne St, Houston, TX, 77004, USA.
⁵² Division of Gynecologic Oncology, Department of Obstetrics And Gynecology, NYU Langone Medical Center, 240 East 38th Street, New York, NY, 10016, USA.
⁵³ Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 417 East 68th Street, New York, NY, 10065, USA.
⁵⁴ Department of Public Health Sciences, The University of Virginia, Box 800717, Charlotteville, VA, 22908, USA.
⁵⁵ Department of Obstetrics and Gynecology, Duke University Medical Center, 25171 Morris Bldg, Durham, NC, 27710, USA.
⁵⁶ Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, 221 Longwood Avenue, Richardson Fuller Building, Boston, MA, 02115, USA.
⁵⁷ Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA.
⁵⁸ Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08903, USA.
⁵⁹ Rutgers School of Public Health, 683 Hoes Lane West, Piscataway, NJ, 08854, USA.
⁶⁰ Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 485 Lexington Ave, New York, NY, 10017, USA.
⁶¹ Department of Obstetrics and Gynecology, Haukeland University Hospital, Kvinneklinikken, Jonas Liesvei 72, 5058, Bergen, Norway.
⁶² Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Postboks 7804, N-5020, Bergen, Norway.
⁶³ Radboud University Medical Center, Radboud Institute for Health Sciences, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
⁶⁴ Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Gynaecology, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
⁶⁵ Department of Obstetrics & Gynecology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
⁶⁶ Knight Cancer Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
⁶⁷ Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, 2703 Frontier Ave NE, Albuquerque, NM, 87131, USA.
⁶⁸ Cancer Control Research, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada.
⁶⁹ Department of Medicine, University of British Columbia, 2775 Laurel Street, Vancouver, BC, V5Z 1M9, Canada.
⁷⁰ Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada.
⁷¹ Department of Biomedical Physiology and Kinesiology, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada.
⁷² Department of Public Health Sciences, Medical University of South Carolina, 68 President Street, Bioengineering Building, Charleston, SC, 29425, USA.
⁷³ International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, ul. Połabska 4, Szczecin, 70-115, Poland.
⁷⁴ Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, ul. Powstańców Wlkp 72, 70-111, Szczecin, Poland.
⁷⁵ Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA.
⁷⁶ Department of Cancer Epidemiology and Prevention, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Wawelska 15B, 02-034, Warsaw, Poland.
⁷⁷ Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, St Andrews Place, Melbourne, VIC 3002, Australia.
⁷⁸ Department of Pathology, University of Melbourne, Grattan Street, Carlton, VIC, 3053, Australia.
⁷⁹ Faculty of Medicine, Southampton University Hospitals Trust, Princess Anne Hospital, University of Southampton, Southampton, SO16 5YA, UK.
⁸⁰ Cancer Research UK Clinical Trials Unit Glasgow, Institute of Cancer Sciences, University of Glasgow, 1053 Gt. Western Road, Glasgow, G12 0YN, UK.
⁸¹ The Beatson West of Scotland Cancer Centre, 1053 Gt. Western Road, Glasgow, G12 0YN, UK.
⁸² Department of Gynaecological Oncology, Glasgow Royal Infirmary, Alexandra Parade, Glasgow, G31 2ER, UK.
⁸³ Department of Health Research and Policy-Epidemiology, Stanford University School of Medicine, HRP Redwood Building, 259 Campus Drive, Stanford, CA, 94305, USA.
⁸⁴ Departments of Population Health Science & Policy and Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA.
⁸⁵ Women's College Research Institute, University of Toronto, 790 Bay Street, Toronto, ON, M5G 1N8, Canada.
⁸⁶ Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
⁸⁷ Department of Chronic Disease Epidemiology, Yale School of Public Health, LEPH 413, 60 College Street, New Haven, CT, 06510, USA.
⁸⁸ Public Health Ontario, 480 University Avenue (/300), Toronto, ON, M5G1V2, Canada.
⁸⁹ Department of Epidemiology, University of California Irvine, 224 Irvine Hall, Irvine, CA, 92697-7550, USA.
⁹⁰ Genetic Epidemiology Research Institute, UCI Center for Cancer Genetics Research & Prevention, School of Medicine, University of California Irvine, 224 Irvine Hall, Irvine, CA, 92697-7550, USA.
⁹¹ Women's Cancer, Institute for Women's Health, University College London, Maple House 1st Floor, 149 Tottenham Court Road, London, W1T 7DN, UK.
⁹² Center for Cancer Prevention and Translational Genomics, Samuel Oschin Cancer Institute, Spielberg Building, 8725 Alden Dr., Los Angeles, CA, 90048, USA.
⁹³ School of Women's and Children's Health, University of New South Wales, Level 1, Women's Health Institute, Royal Hospital for Women, Barker Street, Randwick, NSW, 2031, Australia.
⁹⁴ The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
⁹⁵ Department of Pathology and Laboratory Diagnostics, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland.

PMID: 29555990
PMCID: PMC5931085
DOI: 10.1038/s41416-018-0011-3

Meta-Analysis

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

Suzanne C Dixon-Suen et al. Br J Cancer. 2018 Apr.

. 2018 Apr;118(8):1123-1129.

doi: 10.1038/s41416-018-0011-3. Epub 2018 Mar 20.

Authors

Affiliations

¹ Gynaecological Cancers Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD 4006, Australia. Suzanne.Dixon@qimrberghofer.edu.au.
² The University of Queensland, School of Public Health, Level 2 Public Health Building (887), Corner of Herston Road & Wyndham Street, Brisbane, QLD 4006, Australia. Suzanne.Dixon@qimrberghofer.edu.au.
³ Gynaecological Cancers Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD 4006, Australia.
⁴ The University of Queensland, School of Public Health, Level 2 Public Health Building (887), Corner of Herston Road & Wyndham Street, Brisbane, QLD 4006, Australia.
⁵ Department of Medicine and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
⁶ Strangeways Research Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health & Primary Care/Department of Oncology, University of Cambridge, Worts Causeway, Cambridge, CB1 8RN, UK.
⁷ Department of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights, SPH Tower, Ann Arbor, MI, 48109-2029, USA.
⁸ Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA, 90033, USA.
⁹ Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, 2525 West End Ave., Nashville, TN, 37203, USA.
¹⁰ Cancer Genetics Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD 4006, Australia.
¹¹ Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA.
¹² Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Universitätsstrasse 21-23, 91054, Erlangen, Germany.
¹³ Vesalius Research Center, VIB, Herestraat 49, bus 912, 3000, Leuven, Belgium.
¹⁴ Laboratory for Translational Genetics, Department of Oncology, University of Leuven, O&N IV Herestraat 49-Box 912, 3000, Leuven, Belgium.
¹⁵ Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Herestraat 49, Leuven, 3000, Belgium.
¹⁶ Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA, 98109-1024, USA.
¹⁷ Department of Epidemiology, University of Washington, 1959 NE Pacific Street, Health Sciences Bldg, F-262, Seattle, WA, 98195, USA.
¹⁸ Department of Epidemiology, The Geisel School of Medicine at Dartmouth, 1 Medical Center Drive, 7927 Rubin Building, Lebanon, NH, 03756, USA.
¹⁹ Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 581, Heidelberg, 69120, Germany.
²⁰ University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
²¹ Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
²² Department of Gynecological Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
²³ Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA, 90048, USA.
²⁴ Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA, 90048, USA.
²⁵ Cancer Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA.
²⁶ Clinics of Obstetrics and Gynaecology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625, Hannover, Germany.
²⁷ Radiation Oncology Research Unit, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625, Hannover, Germany.
²⁸ Department of Pathology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 8, 00029, Helsinki, Finland.
²⁹ Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 8, 00029, Helsinki, Finland.
³⁰ Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, 300 Halket Street, Pittsburgh, PA, 15213, USA.
³¹ Ovarian Cancer Center of Excellence, Women's Cancer Research Program, Magee-Women's Research Institute and University of Pittsburgh Cancer Institute, 204 Craft Avenue, Pittsburgh, PA, 15213, USA.
³² Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, 130 De Soto Street, Pittsburgh, PA, 15261, USA.
³³ The University of Texas Health Science Center at Houston, School of Public Health, 1200 Herman Pressler, Suite E-1015, Houston, TX, 77030, USA.
³⁴ Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/ Evang. Huyssens-Stiftung/ Knappschaft GmbH, Henricistrasse 92, 45136, Essen, Germany.
³⁵ Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Ludwig-Erhard-Strasse 100, 65199, Wiesbaden, Germany.
³⁶ Praxis für Humangenetik, Biebricher Allee 117, 65187, Wiesbaden, Germany.
³⁷ Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8635 West Third Street, Los Angeles, CA, 90048, USA.
³⁸ Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100, Copenhagen, Denmark.
³⁹ Department of Gynaecology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
⁴⁰ Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2370, Herlev, Denmark.
⁴¹ Department of Health Science Research, Division of Epidemiology, Mayo Clinic, 200 First Street SW, Charlton 6, Rochester, MN, 55905, USA.
⁴² Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
⁴³ Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Stabile 13, Rochester, MN, 55905, USA.
⁴⁴ Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, 200 First Street SW, Charlton 6, Rochester, MN, 55905, USA.
⁴⁵ Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC 3004, Australia.
⁴⁶ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Grattan Street, Parkville, VIC 3010, Australia.
⁴⁷ Department of Epidemiology and Preventive Medicine, Monash University, The Alfred Centre, 99 Commercial Road, Melbourne, VIC 3004, Australia.
⁴⁸ Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Grattan Street, Carlton, VIC 3053, Australia.
⁴⁹ Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1155 Pressler Blvd-Unit 1340, Houston, TX, 77030, USA.
⁵⁰ Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1155 Pressler Blvd - Unit 1340, Houston, TX, 77030, USA.
⁵¹ College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne St, Houston, TX, 77004, USA.
⁵² Division of Gynecologic Oncology, Department of Obstetrics And Gynecology, NYU Langone Medical Center, 240 East 38th Street, New York, NY, 10016, USA.
⁵³ Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 417 East 68th Street, New York, NY, 10065, USA.
⁵⁴ Department of Public Health Sciences, The University of Virginia, Box 800717, Charlotteville, VA, 22908, USA.
⁵⁵ Department of Obstetrics and Gynecology, Duke University Medical Center, 25171 Morris Bldg, Durham, NC, 27710, USA.
⁵⁶ Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, 221 Longwood Avenue, Richardson Fuller Building, Boston, MA, 02115, USA.
⁵⁷ Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA.
⁵⁸ Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08903, USA.
⁵⁹ Rutgers School of Public Health, 683 Hoes Lane West, Piscataway, NJ, 08854, USA.
⁶⁰ Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 485 Lexington Ave, New York, NY, 10017, USA.
⁶¹ Department of Obstetrics and Gynecology, Haukeland University Hospital, Kvinneklinikken, Jonas Liesvei 72, 5058, Bergen, Norway.
⁶² Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Postboks 7804, N-5020, Bergen, Norway.
⁶³ Radboud University Medical Center, Radboud Institute for Health Sciences, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
⁶⁴ Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Gynaecology, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
⁶⁵ Department of Obstetrics & Gynecology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
⁶⁶ Knight Cancer Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
⁶⁷ Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, 2703 Frontier Ave NE, Albuquerque, NM, 87131, USA.
⁶⁸ Cancer Control Research, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada.
⁶⁹ Department of Medicine, University of British Columbia, 2775 Laurel Street, Vancouver, BC, V5Z 1M9, Canada.
⁷⁰ Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada.
⁷¹ Department of Biomedical Physiology and Kinesiology, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada.
⁷² Department of Public Health Sciences, Medical University of South Carolina, 68 President Street, Bioengineering Building, Charleston, SC, 29425, USA.
⁷³ International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, ul. Połabska 4, Szczecin, 70-115, Poland.
⁷⁴ Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, ul. Powstańców Wlkp 72, 70-111, Szczecin, Poland.
⁷⁵ Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA.
⁷⁶ Department of Cancer Epidemiology and Prevention, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Wawelska 15B, 02-034, Warsaw, Poland.
⁷⁷ Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, St Andrews Place, Melbourne, VIC 3002, Australia.
⁷⁸ Department of Pathology, University of Melbourne, Grattan Street, Carlton, VIC, 3053, Australia.
⁷⁹ Faculty of Medicine, Southampton University Hospitals Trust, Princess Anne Hospital, University of Southampton, Southampton, SO16 5YA, UK.
⁸⁰ Cancer Research UK Clinical Trials Unit Glasgow, Institute of Cancer Sciences, University of Glasgow, 1053 Gt. Western Road, Glasgow, G12 0YN, UK.
⁸¹ The Beatson West of Scotland Cancer Centre, 1053 Gt. Western Road, Glasgow, G12 0YN, UK.
⁸² Department of Gynaecological Oncology, Glasgow Royal Infirmary, Alexandra Parade, Glasgow, G31 2ER, UK.
⁸³ Department of Health Research and Policy-Epidemiology, Stanford University School of Medicine, HRP Redwood Building, 259 Campus Drive, Stanford, CA, 94305, USA.
⁸⁴ Departments of Population Health Science & Policy and Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA.
⁸⁵ Women's College Research Institute, University of Toronto, 790 Bay Street, Toronto, ON, M5G 1N8, Canada.
⁸⁶ Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
⁸⁷ Department of Chronic Disease Epidemiology, Yale School of Public Health, LEPH 413, 60 College Street, New Haven, CT, 06510, USA.
⁸⁸ Public Health Ontario, 480 University Avenue (/300), Toronto, ON, M5G1V2, Canada.
⁸⁹ Department of Epidemiology, University of California Irvine, 224 Irvine Hall, Irvine, CA, 92697-7550, USA.
⁹⁰ Genetic Epidemiology Research Institute, UCI Center for Cancer Genetics Research & Prevention, School of Medicine, University of California Irvine, 224 Irvine Hall, Irvine, CA, 92697-7550, USA.
⁹¹ Women's Cancer, Institute for Women's Health, University College London, Maple House 1st Floor, 149 Tottenham Court Road, London, W1T 7DN, UK.
⁹² Center for Cancer Prevention and Translational Genomics, Samuel Oschin Cancer Institute, Spielberg Building, 8725 Alden Dr., Los Angeles, CA, 90048, USA.
⁹³ School of Women's and Children's Health, University of New South Wales, Level 1, Women's Health Institute, Royal Hospital for Women, Barker Street, Randwick, NSW, 2031, Australia.
⁹⁴ The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
⁹⁵ Department of Pathology and Laboratory Diagnostics, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland.

PMID: 29555990
PMCID: PMC5931085
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.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

**Fig. 1**
Association between increasing genetically predicted height and risks of all, invasive and borderline ovarian tumours. Increasing height per 5 cm predicted by weighted 609-locus genetic risk score among 39 studies. Risk of a all, b invasive and c borderline ovarian tumours. The UK grouping includes RMH, SOC, SRO, UKR, SEA and UKO for a and b, and RMH, SOC and SEA for c

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References

1. Emerging Risk Factors Collaboration. Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis. Int. J. Epidemiol. 2012;41:1419–1433. doi: 10.1093/ije/dys086. - DOI - PMC - PubMed
1. Schouten LJ, et al. Height, body mass index, and ovarian cancer: a pooled analysis of 12 cohort studies. Cancer Epidemiol. Biomark. Prev. 2008;17:902–912. doi: 10.1158/1055-9965.EPI-07-2524. - DOI - PMC - PubMed
1. World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of OvarianCancer 2014. Washington DC: AICR; 2014.
1. Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and body size: individual participant meta-analysis including 25,157 women with ovarian cancer from 47 epidemiological studies. PLoS Med. 2012;9:e1001200. doi: 10.1371/journal.pmed.1001200. - DOI - PMC - PubMed
1. Davey Smith G, Ebrahim S. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int. J. Epidemiol. 2003;32:1–22. doi: 10.1093/ije/dyg070. - DOI - PubMed

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[1] Emerging Risk Factors Collaboration. Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis. Int. J. Epidemiol. 2012;41:1419–1433. doi: 10.1093/ije/dys086. - DOI - PMC - PubMed

[2] Emerging Risk Factors Collaboration. Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis. Int. J. Epidemiol. 2012;41:1419–1433. doi: 10.1093/ije/dys086. - DOI - PMC - PubMed

[3] Schouten LJ, et al. Height, body mass index, and ovarian cancer: a pooled analysis of 12 cohort studies. Cancer Epidemiol. Biomark. Prev. 2008;17:902–912. doi: 10.1158/1055-9965.EPI-07-2524. - DOI - PMC - PubMed

[4] Schouten LJ, et al. Height, body mass index, and ovarian cancer: a pooled analysis of 12 cohort studies. Cancer Epidemiol. Biomark. Prev. 2008;17:902–912. doi: 10.1158/1055-9965.EPI-07-2524. - DOI - PMC - PubMed

[5] World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of OvarianCancer 2014. Washington DC: AICR; 2014.

[6] World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of OvarianCancer 2014. Washington DC: AICR; 2014.

[7] Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and body size: individual participant meta-analysis including 25,157 women with ovarian cancer from 47 epidemiological studies. PLoS Med. 2012;9:e1001200. doi: 10.1371/journal.pmed.1001200. - DOI - PMC - PubMed

[8] Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and body size: individual participant meta-analysis including 25,157 women with ovarian cancer from 47 epidemiological studies. PLoS Med. 2012;9:e1001200. doi: 10.1371/journal.pmed.1001200. - DOI - PMC - PubMed

[9] Davey Smith G, Ebrahim S. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int. J. Epidemiol. 2003;32:1–22. doi: 10.1093/ije/dyg070. - DOI - PubMed

[10] Davey Smith G, Ebrahim S. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int. J. Epidemiol. 2003;32:1–22. doi: 10.1093/ije/dyg070. - DOI - PubMed

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

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

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