Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study

Ong JS, Cuellar-Partida G, Lu Y, Australian Ovarian Cancer Study, Fasching PA, Hein A, Burghaus S, Beckmann MW, Lambrechts D, Van Nieuwenhuysen E, Vergote I, Vanderstichele A, Anne Doherty J, Anne Rossing M, Chang-Claude J, Eilber U, Rudolph A, Wang-Gohrke S, Goodman MT, Bogdanova N, Dörk T, Dürst 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, Høgdall E, Høgdall CK, Jensen A, Giles GG, Bruinsma F, Kjaer SK, Hildebrandt MA, Liang D, Lu KH, Wu X, Bisogna M, Dao F, Levine DA, Cramer DW, Terry KL, Tworoger SS, Stampfer M, Missmer S, Bjorge L, Salvesen HB, Kopperud RK, Bischof K, Aben KK, Kiemeney LA, Massuger LF, Brooks-Wilson A, Olson SH, McGuire V, Rothstein JH, Sieh W, Whittemore AS, Cook LS, Le ND, Gilks CB, Gronwald J, Jakubowska A, Lubiński J, Kluz T, 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, Campbell I, 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, Pearce CL, Berchuck A, Pharoah PD, Chenevix-Trench G, Gharahkhani P, Neale RE, Webb PM, MacGregor S

International journal of epidemiology · 93 citas

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Cómo se estudió

Diseño: Estudio de casos y controles (clasificado por nuestro filtro de IA)
Estudiado en: Personas
Resultado principal: Eventos clínicos como enfermedad o muerte

Quién lo pagó

Financiación: Financiado por la industria
Organización sin fines de lucro: Ovarian Cancer Research Fund
Empresa: Amgen
Universidad u hospital: Francis Crick Institute
Organización sin fines de lucro: Cancer Research UK
Gobierno: National Institute for Health and Care Research
Gobierno: European Commission
Empresa: Johnson and Johnson
Gobierno: National Cancer Institute
Gobierno: National Center for Research Resources
Universidad u hospital: The Francis Crick Institute
Gobierno: NCI NIH HHS
Gobierno: National Institute for Health Research (NIHR)
Gobierno: NCRR NIH HHS
Subvenciones: National Cancer Institute (P30 CA-016672); National Cancer Institute (K07 CA 095666); National Cancer Institute (R01‐CA050385); National Cancer Institute (R01-CA063682); National Cancer Institute (P30CA046592.); National Cancer Institute (R01‐CA087538); National Cancer Institute (R01‐CA074850); National Cancer Institute (R01CA063678); National Cancer Institute (R01‐CA083918); Cancer Research UK (10119); National Cancer Institute (P50-CA-105009); National Cancer Institute (R01-CA-112523); National Cancer Institute (R01CA126841); National Cancer Institute (#P30 CA016056); National Cancer Institute (R03CA115195); National Cancer Institute (UM1 CA186107); National Cancer Institute (N01CN025403); National Cancer Institute (R03 CA113148); National Center for Research Resources (M01 RR-000056); National Cancer Institute (K22CA138563); National Cancer Institute (P50‐CA159981); Cancer Research UK (16561); National Cancer Institute (P01-CA017054); National Cancer Institute (N01‐PC035137); National Cancer Institute (R01‐CA058860); National Cancer Institute (R01 CA054419); National Cancer Institute (UM1 CA176726); Cancer Research UK (C490/A6187); National Cancer Institute (P01CA087969); National Cancer Institute (U19 CA148112); National Cancer Institute (K07CA080668); National Cancer Institute (R01-CA149429); National Cancer Institute (R01‐CA049449); National Cancer Institute (R01‐CA067262); National Cancer Institute (R01CA136924); National Cancer Institute (R01CA058598); National Cancer Institute (R01CA087696); National Cancer Institute (K07CA143047); Cancer Research UK (10124); National Cancer Institute (P50CA136393); National Cancer Institute (R01CA095023); National Cancer Institute (K07 CA092044); Francis Crick Institute (10124); National Cancer Institute (R01CA122443); Francis Crick Institute (10119); National Cancer Institute (N01 PC067010); European Commission (223175); National Cancer Institute (P30CA008748); National Cancer Institute (P30CA072720); National Cancer Institute (P30CA015083); National Cancer Institute (P30CA076292); National Cancer Institute (P30CA014089); National Cancer Institute (U01-CA069417); National Cancer Institute (R01-CA-114343)

Según 13 financiadores declarados.

Publicación

Publicado: 2016-09-04 · Int J Epidemiol · vol. 45 · número 5 · págs. 1619–1630
Editorial: Oxford University Press
Citado: 136 citas · más que el 99% de estudios similares · 14.3× el promedio de su campo
Impacto: Entre el 10 % más citado de su campo
Referencias: 46 trabajos
Acceso: Lectura gratuita
Áreas de investigación: Vitamin D Research Studies · Genetic Associations and Epidemiology · Ovarian cancer diagnosis and treatment
Palabras clave: vitamin D, 25-hydroxyvitamin D, ovarian cancer, high-grade serous ovarian cancer, circulating vitamin D levels, genetic variants, DHCR7, CYP2R1, GC gene, cancer risk, confounding in observational studies
MeSH: humans, neoplasms, glandular and epithelial, ovarian neoplasms, genetic predisposition to disease, vitamin d, odds ratio, risk factors, polymorphism, single nucleotide, female, mendelian randomization analysis, carcinoma, ovarian epithelial

DOI ↗PubMed Central ↗OpenAlex ↗

100 autores

Jue‐Sheng Ong🇦🇺The University of Queensland; QIMR Berghofer Medical Research Institute
Gabriel Cuéllar-Partida🇦🇺The University of Queensland; QIMR Berghofer Medical Research Institute
Yi Lu🇦🇺QIMR Berghofer Medical Research Institute
Australian Ovarian Cancer Study🇺🇸🇩🇪University of California, Los Angeles; Friedrich-Alexander-Universität Erlangen-Nürnberg; Universitätsklinikum Erlangen; Comprehensive Cancer Center Erlangen
Peter Andreas Fasching🇺🇸🇩🇪University of California, Los Angeles; Friedrich-Alexander-Universität Erlangen-Nürnberg; Universitätsklinikum Erlangen; Comprehensive Cancer Center Erlangen
Alexander Hein🇩🇪Friedrich-Alexander-Universität Erlangen-Nürnberg; Universitätsklinikum Erlangen; Comprehensive Cancer Center Erlangen
Stefanie Burghaus🇩🇪Friedrich-Alexander-Universität Erlangen-Nürnberg; Universitätsklinikum Erlangen; Comprehensive Cancer Center Erlangen
Matthias W. Beckmann🇩🇪🇧🇪Friedrich-Alexander-Universität Erlangen-Nürnberg; Universitätsklinikum Erlangen; Comprehensive Cancer Center Erlangen; KU Leuven
Diether Lambrechts🇧🇪Universitair Ziekenhuis Leuven; KU Leuven
Els Van Nieuwenhuysen🇧🇪Universitair Ziekenhuis Leuven
Ignace B. Vergote🇧🇪Universitair Ziekenhuis Leuven
Adriaan Vanderstichele🇦🇺🇧🇪The University of Queensland; QIMR Berghofer Medical Research Institute; Universitair Ziekenhuis Leuven
Jennifer A. Doherty🇦🇺🇺🇸The University of Queensland; University of Washington; QIMR Berghofer Medical Research Institute; Fred Hutch Cancer Center
Mary Anne Rossing🇩🇪🇺🇸German Cancer Research Center; University of Washington; Fred Hutch Cancer Center
Jenny C. Chang-Claude🇩🇪German Cancer Research Center
Ursula Eilber🇩🇪German Cancer Research Center
Anja Rudolph🇩🇪German Cancer Research Center; Universität Ulm
Shan Wang‐Gohrke🇺🇸🇩🇪Cedars-Sinai Medical Center; Universität Ulm
Marc T. Goodman🇺🇸🇩🇪Cedars-Sinai Medical Center; Medizinische Hochschule Hannover
Natalia Viktorovna Bogdanova🇩🇪Medizinische Hochschule Hannover
Thilo Dörk🇩🇪Medizinische Hochschule Hannover; Jena University Hospital; Friedrich Schiller University Jena
Matthias Dürst🇩🇪Medizinische Hochschule Hannover; Jena University Hospital; Friedrich Schiller University Jena
Peter Hillemanns🇩🇪Medizinische Hochschule Hannover; Jena University Hospital; Friedrich Schiller University Jena
Ingo Bernard Runnebaum🇧🇾🇩🇪N.N. Alexandrov National Cancer Centre; Jena University Hospital; Friedrich Schiller University Jena
Natalia Antonenkova🇫🇮🇧🇾University of Helsinki; Helsinki University Hospital; N.N. Alexandrov National Cancer Centre
Ralf C. Bützow🇫🇮University of Helsinki; Helsinki University Hospital
Arto Leminen🇫🇮University of Helsinki; Helsinki University Hospital
Heli A. Nevanlinna🇫🇮University of Helsinki; Helsinki University Hospital
Liisa M. Pelttari🇫🇮🇺🇸University of Helsinki; University of Pittsburgh; Helsinki University Hospital; Magee-Womens Research Institute; UPMC Hillman Cancer Center
Robert P. Edwards🇺🇸University of Pittsburgh; Magee-Womens Research Institute; UPMC Hillman Cancer Center
Joseph Leo Kelley🇺🇸University of Pittsburgh
Francesmary Modugno🇺🇸Roswell Park Comprehensive Cancer Center; University of Pittsburgh
Kirsten B. Moysich🇺🇸Roswell Park Comprehensive Cancer Center; The University of Texas Health Science Center at Houston
Roberta B. Ness🇺🇸Roswell Park Comprehensive Cancer Center
Rikki A. Cannioto🇩🇰🇺🇸University of Copenhagen; Roswell Park Comprehensive Cancer Center; Herlev Hospital; Danish Cancer Society
Estrid Vilma Solyom Høgdall🇩🇰University of Copenhagen; Herlev Hospital; Rigshospitalet; Danish Cancer Society
Claus Kim Høgdall🇩🇰University of Copenhagen; Rigshospitalet; Danish Cancer Society
Allan Jensen🇩🇰Danish Cancer Society
Graham G. Giles🇺🇸🇦🇺Cedars-Sinai Medical Center; Cancer Council Victoria
Fiona Bruinsma🇩🇰🇦🇺University of Copenhagen; Cancer Council Victoria; Rigshospitalet; Danish Cancer Society
Susanne K. Kjær🇩🇰🇺🇸University of Copenhagen; The University of Texas MD Anderson Cancer Center; Rigshospitalet; Danish Cancer Society
Michelle A.T. Hildebrandt🇺🇸The University of Texas MD Anderson Cancer Center; Texas Southern University
Dong Liang🇺🇸The University of Texas MD Anderson Cancer Center; Texas Southern University
Karen H. Lu🇺🇸The University of Texas MD Anderson Cancer Center
Xifeng Wu🇺🇸Memorial Sloan Kettering Cancer Center; The University of Texas MD Anderson Cancer Center
Maria Bisogna🇺🇸Memorial Sloan Kettering Cancer Center
Fanny Dao🇺🇸Memorial Sloan Kettering Cancer Center
Douglas A. Levine🇺🇸Brigham and Women's Hospital; Memorial Sloan Kettering Cancer Center
Daniel William Cramer🇺🇸Brigham and Women's Hospital
Kathryn L. Terry🇺🇸Brigham and Women's Hospital; Harvard University
Shelley S. Tworoger🇺🇸Brigham and Women's Hospital; Harvard University
Meir J. Stampfer🇺🇸Brigham and Women's Hospital; Harvard University
Stacey A. Missmer🇺🇸🇳🇴Cedars-Sinai Medical Center; Haukeland University Hospital; University of Bergen
Line Bjørge🇳🇴Haukeland University Hospital; University of Bergen
Helga Birgitte Salvesen🇳🇴Haukeland University Hospital; University of Bergen
Reidun Kristin Kopperud🇳🇴Haukeland University Hospital; University of Bergen
Katharina Bischof🇳🇱🇳🇴Radboud University Nijmegen; Haukeland University Hospital; Radboud University Medical Center; Netherlands Comprehensive Cancer Organisation; Radboud Institute for Health Sciences; University of Bergen
Katja K.H. Aben🇳🇱Radboud University Nijmegen; Radboud University Medical Center; Netherlands Comprehensive Cancer Organisation; Radboud Institute for Health Sciences
Lambertus A.L.M. Kiemeney🇳🇱Radboud University Nijmegen; Radboud University Medical Center; Radboud Institute for Molecular Life Sciences; Radboud Institute for Health Sciences
Leon F.A.G. Massuger🇨🇦🇳🇱BC Cancer Agency; Radboud University Nijmegen; Simon Fraser University; Radboud University Medical Center; Radboud Institute for Molecular Life Sciences; Canada's Michael Smith Genome Sciences Centre
Angela R Brooks-Wilson🇨🇦🇺🇸BC Cancer Agency; Memorial Sloan Kettering Cancer Center; Simon Fraser University; Canada's Michael Smith Genome Sciences Centre
Sara H. Olson🇺🇸Memorial Sloan Kettering Cancer Center; Stanford Medicine; Stanford University
Valerie McGuire🇺🇸Stanford Medicine; Stanford University
Joseph H. Rothstein🇺🇸Stanford Medicine; Stanford University
Weiva Sieh🇺🇸Stanford Medicine; Stanford University
Alice S. Whittemore🇺🇸University of New Mexico; Stanford Medicine; Stanford University
Linda S. Cook🇨🇦🇺🇸BC Cancer Agency; University of New Mexico
Nhu D. Le🇨🇦BC Cancer Agency; University of British Columbia
C. Blake Gilks🇨🇦🇵🇱University of British Columbia; International Hereditary Cancer Center; Pomeranian Medical University
Jacek Gronwald🇵🇱International Hereditary Cancer Center; Pomeranian Medical University
Anna Jakubowska🇵🇱International Hereditary Cancer Center; Pomeranian Medical University
Jan Lubiński🇵🇱International Hereditary Cancer Center; Pomeranian Medical University; University of Rzeszów
Tomasz Kluz🇬🇧🇵🇱University of Cambridge; University of Rzeszów
Honglin Song🇬🇧University of Cambridge
Jonathan P. Tyrer🇬🇧🇺🇸University of Cambridge; National Cancer Institute; Division of Cancer Epidemiology and Genetics
Nicolas Wentzensen🇺🇸National Cancer Institute; Division of Cancer Epidemiology and Genetics
Louise Annette Brinton🇺🇸National Cancer Institute; Division of Cancer Epidemiology and Genetics
Britton L. Trabert🇺🇸🇵🇱National Cancer Institute; The Maria Sklodowska-Curie National Research Institute of Oncology; Division of Cancer Epidemiology and Genetics
Jolanta Lissowska🇨🇦🇵🇱Public Health Ontario; The Maria Sklodowska-Curie National Research Institute of Oncology
John R McLaughlin🇨🇦University of Toronto; Public Health Ontario
Steven A. Narod🇨🇦🇺🇸University of Toronto; Moffitt Cancer Center
Catherine Phelan🇺🇸University of California, Irvine; Moffitt Cancer Center
Hoda Anton‐Culver🇺🇸University of California, Irvine
Argyrios Ziogas🇺🇸🇬🇧University of California, Irvine; University of Southampton
Diana Eccles🇦🇺🇬🇧Peter MacCallum Cancer Centre; University of Southampton
Ian Campbell🇦🇺🇺🇸Peter MacCallum Cancer Centre; USC Norris Comprehensive Cancer Center
Simon A. Gayther🇺🇸🇬🇧University of Southern California; USC Norris Comprehensive Cancer Center; University College London
Aleksandra Gentry‐Maharaj🇬🇧University College London
Usha Menon🇺🇸🇬🇧USC Norris Comprehensive Cancer Center; University College London
Susan J. Ramus🇺🇸University of Southern California; USC Norris Comprehensive Cancer Center
Anna H. Wu🇺🇸🇵🇱University of Southern California; USC Norris Comprehensive Cancer Center; The Maria Sklodowska-Curie National Research Institute of Oncology
Agnieszka Dansonka‐Mieszkowska🇵🇱Medical University of Warsaw; The Maria Sklodowska-Curie National Research Institute of Oncology
Jolanta Kupryjańczyk🇵🇱Medical University of Warsaw
Agnieszka Timorek🇵🇱Medical University of Warsaw; The Maria Sklodowska-Curie National Research Institute of Oncology
Lukasz M. Szafron🇺🇸🇵🇱Mayo Clinic; The Maria Sklodowska-Curie National Research Institute of Oncology
Julie M. Cunningham🇺🇸Mayo Clinic; University of Kansas
Brooke L. Fridley🇺🇸Mayo Clinic; University of Kansas
Stacey J. Winham🇺🇸Mayo Clinic; Rutgers Cancer Institute
Elisa Victoria Bandera🇺🇸Rutgers, The State University of New Jersey; Brigham and Women's Hospital; Harvard University; Rutgers Cancer Institute
Elizabeth M. Poole🇺🇸Brigham and Women's Hospital; Harvard University; Oregon Health & Science University

Resumen

El texto original del estudio, en el idioma en que se publicó.

Background

In vitro and observational epidemiological studies suggest that vitamin D may play a role in cancer prevention. However, the relationship between vitamin D and ovarian cancer is uncertain, with observational studies generating conflicting findings. A potential limitation of observational studies is inadequate control of confounding. To overcome this problem, we used Mendelian randomization (MR) to evaluate the association between single nucleotide polymorphisms (SNPs) associated with circulating 25-hydroxyvitamin D [25(OH)D] concentration and risk of ovarian cancer.

Methods

We employed SNPs with well-established associations with 25(OH)D concentration as instrumental variables for MR: rs7944926 (DHCR7), rs12794714 (CYP2R1) and rs2282679 (GC). We included 31 719 women of European ancestry (10 065 cases, 21 654 controls) from the Ovarian Cancer Association Consortium, who were genotyped using customized Illumina Infinium iSelect (iCOGS) arrays. A two-sample (summary data) MR approach was used and analyses were performed separately for all ovarian cancer (10 065 cases) and for high-grade serous ovarian cancer (4121 cases).

Results

The odds ratio for epithelial ovarian cancer risk (10 065 cases) estimated by combining the individual SNP associations using inverse variance weighting was 1.27 (95% confidence interval: 1.06 to 1.51) per 20 nmol/L decrease in 25(OH)D concentration. The estimated odds ratio for high-grade serous epithelial ovarian cancer (4121 cases) was 1.54 (1.19, 2.01).

Conclusions

Genetically lowered 25-hydroxyvitamin D concentrations were associated with higher ovarian cancer susceptibility in Europeans. These findings suggest that increasing plasma vitamin D levels may reduce risk of ovarian cancer.

Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.

Leer el texto completo ↗Ver en PubMed ↗

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