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

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 (2016)


Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 45

Pages Range: 1619-1630

Journal Issue: 5

DOI: 10.1093/ije/dyw207

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.

Authors with CRIS profile

Involved external institutions

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

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://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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