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

Journal article


Publication Details

Author(s): Ong JS, Cuellar-Partida G, Lu Y, Fasching PA, Hein A, Burghaus S, Beckmann M, Lambrechts D, Van Nieuwenhuysen E, Vergote I, Vanderstichele A, Doherty JA, Rossing MA, Chang-Claude J, Eilber U, Rudolph A, Wang-Gohrke S, Goodman MT, Bogdanova N, Dork T, Durst 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, Hogdall CK, 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, Stampfer M, 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, 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 PDP, Chenevix-Trench G, Gharahkhani P, Neale RE, Webb PM, Macgregor S
Journal: International Journal of Epidemiology
Publication year: 2016
Volume: 45
Journal issue: 5
Pages range: 1619-1630
ISSN: 0300-5771


Abstract

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.


FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Burghaus, Stefanie Dr. med.
Frauenklinik
Hein, Alexander PD Dr.
Frauenklinik


External institutions with authors

Brigham and Women's Hospital (BWH)
British Columbia Cancer Agency
Cancer Council Victoria
Cedars-Sinai Medical Center
Danish Cancer Society Research Center
Dartmouth College
Deutsches Krebsforschungszentrum (DKFZ)
Duke University
Friedrich-Schiller-Universität Jena
Hannover Medical School / Medizinische Hochschule Hannover (MHH)
Harvard University
Haukeland University Hospital / Haukeland universitetssykehus
Helsingin yliopisto / University of Helsinki
Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS)
H. Lee Moffitt Cancer Center & Research Institute
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie
Mayo Clinic
Memorial Sloan Kettering Cancer Center
Monash University
National Cancer Institute (NCI)
N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology
Oregon Health and Science University (OSHU)
Peter MacCallum Cancer Centre
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
Public Health Ontario
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Radboud University Nijmegen
Roswell Park Cancer Institute
Rutgers Cancer Institute of New Jersey
Stanford University
Texas Southern University (TSU)
Universität Ulm
University College London (UCL)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of British Columbia
University of California Irvine
University of California Los Angeles (UCLA)
University of Cambridge
University of Copenhagen
University of Kansas (KU)
University of New Mexico
University of Pittsburgh
University of Southampton
University of Southern California (USC)
University of Texas MD Anderson Cancer Center
University of Toronto
University of Washington
Uniwersytet Rzeszowski
Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu


How to cite

APA:
Ong, J.-S., Cuellar-Partida, G., Lu, Y., Fasching, P.A., Hein, A., Burghaus, S.,... Macgregor, S. (2016). Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study. International Journal of Epidemiology, 45(5), 1619-1630. https://dx.doi.org/10.1093/ije/dyw207

MLA:
Ong, Jue-Sheng, et al. "Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study." International Journal of Epidemiology 45.5 (2016): 1619-1630.

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Last updated on 2018-10-11 at 02:08