Format

Send to

Choose Destination
Br J Cancer. 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.

Dixon-Suen SC1,2, Nagle CM3,4, Thrift AP5, Pharoah PDP6, Ewing A6, Pearce CL7,8, Zheng W9; Australian Ovarian Cancer Study Group, Chenevix-Trench G10, Fasching PA11,12, Beckmann MW12, Lambrechts D13,14, Vergote I15, Lambrechts S15, Van Nieuwenhuysen E15, Rossing MA16,17, Doherty JA18, Wicklund KG16, Chang-Claude J19,20, Jung AY19, Moysich KB21, Odunsi K22, Goodman MT23,24, Wilkens LR25, Thompson PJ23, Shvetsov YB25, Dörk T26, Park-Simon TW26, Hillemanns P26, Bogdanova N27, Butzow R28, Nevanlinna H29, Pelttari LM29, Leminen A29, Modugno F30,31,32, Ness RB33, Edwards RP30,31, Kelley JL30, Heitz F34,35, du Bois A34,35, Harter P34,35, Schwaab I36, Karlan BY37, Lester J37, Orsulic S37, Rimel BJ37, Kjær SK38,39, Høgdall E38,40, Jensen A38, Goode EL41, Fridley BL42, Cunningham JM43, Winham SJ44, Giles GG45,46,47, Bruinsma F45, Milne RL45,46, Southey MC48, Hildebrandt MAT49, Wu X49, Lu KH50, Liang D51, Levine DA52, Bisogna M53, Schildkraut JM54, Berchuck A55, Cramer DW56, Terry KL56,57, Bandera EV58,59, Olson SH60, Salvesen HB61,62, Thomsen LCV61,62, Kopperud RK61,62, Bjorge L61,62, Kiemeney LA63, Massuger LFAG64, Pejovic T65,66, Bruegl A65, Cook LS67, Le ND68, Swenerton KD69, Brooks-Wilson A70,71, Kelemen LE72, Lubiński J73, Huzarski T73, Gronwald J73, Menkiszak J74, Wentzensen N75, Brinton L75, Yang H75, Lissowska J76, Høgdall CK39, Lundvall L39, Song H6, Tyrer JP6, Campbell I77,78, Eccles D79, Paul J80, Glasspool R81, Siddiqui N82, Whittemore AS83, Sieh W84, McGuire V83, Rothstein JH84, Narod SA85, Phelan C86, Risch HA87, McLaughlin JR88, Anton-Culver H89,90, Ziogas A89, Menon U91, Gayther SA92, Ramus SJ93,94, Gentry-Maharaj A91, Wu AH8, Pike MC8,60, Tseng CC8, Kupryjanczyk J95, Dansonka-Mieszkowska A95, Budzilowska A95, Rzepecka IK95, Webb PM3,4; Ovarian Cancer Association Consortium.

Author information

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.

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.

PMID:
29555990
PMCID:
PMC5931085
DOI:
10.1038/s41416-018-0011-3
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Grant support

Publication types

MeSH terms

Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center