Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study
Jue-Sheng Ong,
Jue‐Sheng Ong,
Gabriel Cuéllar-Partida,
Gabriel Cuellar-Partida,
Lu Y,
Yi Lu,
Australian Ovarian Cancer Study,
Peter A. Fasching,
Fasching PA,
Alexander Hein,
Stefanie Burghaus,
Beckmann MW,
Matthias W. Beckmann,
Diether Lambrechts,
Van Nieuwenhuysen E,
Els Van Nieuwenhuysen,
Ignace Vergote,
Vergote I,
Adriaan Vanderstichele,
Jennifer Anne Doherty,
Anne Doherty J,
Mary Anne Rossing,
Anne Rossing M,
Jenny Chang-Claude,
Chang-Claude J,
Ursula Eilber,
Eilber U,
Rudolph A,
Anja Rudolph,
Shan Wang-Gohrke,
Wang-Gohrke S,
Marc T. Goodman,
Natalia Bogdanova,
Thilo Dörk,
Matthias Dürst,
Dürst M,
Peter Hillemanns,
Runnebaum IB,
Ingo B. Runnebaum,
Antonenkova N,
Natalia Antonenkova,
Ralf Butzow,
Butzow R,
Arto Leminen,
Leminen A,
Heli Nevanlinna,
Nevanlinna H,
Liisa M. Pelttari,
Robert P. Edwards,
Edwards RP,
Kelley JL,
Joseph L. Kelley,
Modugno F,
Francesmary Modugno,
Moysich KB,
Kirsten B. Moysich,
Roberta B. Ness,
Ness RB,
Rikki Cannioto,
Cannioto R,
Estrid Høgdall,
Høgdall E,
Claus K Høgdall,
Høgdall CK,
Allan Jensen,
Graham G. Giles,
Giles GG,
Fiona Bruinsma,
Susanne K Kjaer,
Kjaer SK,
Michelle A.T. Hildebrandt,
Hildebrandt MA,
Dong Liang,
Karen H. Lu,
Lu KH,
Wu X,
Xifeng Wu,
Bisogna M,
Maria Bisogna,
Fanny Dao,
Dao F,
Douglas A. Levine,
Cramer DW,
Daniel W. Cramer,
Kathryn L. Terry,
Shelley S. Tworoger,
Stampfer M,
Meir Stampfer,
Stacey Missmer,
Missmer S,
Line Bjorge,
Bjorge L,
Helga B. Salvesen,
Salvesen HB,
Reidun K Kopperud,
Kopperud RK,
Bischof K,
Katharina Bischof,
Katja K.H. Aben,
Lambertus A. Kiemeney,
Massuger LF,
Leon F.A.G. Massuger,
Brooks-Wilson A,
Angela Brooks-Wilson,
Sara H. Olson,
McGuire V,
Valerie McGuire,
Rothstein JH,
Joseph H. Rothstein,
Weiva Sieh,
Alice S. Whittemore,
Whittemore AS,
Linda S. Cook,
Cook LS,
Nhu D. Le,
Le ND,
C. Blake Gilks,
Gilks CB,
Gronwald J,
Jacek Gronwald,
Anna Jakubowska,
Jan Lubiński,
Tomasz Kluz,
Honglin Song,
Song H,
Tyrer JP,
Jonathan P. Tyrer,
Wentzensen N,
Nicolas Wentzensen,
Louise Brinton,
Brinton L,
Britton Trabert,
Jolanta Lissowska,
John R. Mclaughlin,
McLaughlin JR,
Steven A. Narod,
Narod SA,
Catherine Phelan,
Phelan C,
Anton-Culver H,
Hoda Anton-Culver,
Ziogas A,
Argyrios Ziogas,
Diana Eccles,
Ian Campbell,
Gayther SA,
Simon A. Gayther,
Gentry-Maharaj A,
Aleksandra Gentry-Maharaj,
Usha Menon,
Susan J. Ramus,
Anna H. Wu,
Wu AH,
Agnieszka Dansonka-Mieszkowska,
Agnieszka Dansonka‐Mieszkowska,
Jolanta Kupryjańczyk,
Jolanta Kupryjanczyk,
Timorek A,
Agnieszka Timorek,
Lukasz Szafron,
Lukasz M. Szafron,
Julie M. Cunningham,
Cunningham JM,
Fridley BL,
Brooke L. Fridley,
Stacey J. Winham,
Elisa V. Bandera,
Bandera EV,
Poole EM,
Elizabeth M. Poole,
Terry K. Morgan,
Morgan TK,
Harvey A. Risch,
Risch HA,
Ellen L. Goode,
Goode EL,
Joellen M. Schildkraut,
Schildkraut JM,
Pearce CL,
Celeste L Pearce,
Berchuck A,
Andrew Berchuck,
Pharoah PD,
Paul D.P. Pharoah,
Georgia Chenevix-Trench,
Georgia Chenevix‐Trench,
Puya Gharahkhani,
Gharahkhani P,
Rachel E Neale,
Neale RE,
Penelope M. Webb,
Stuart MacGregor
Other
OA: closed
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AI-generated summary
by gemini-2.5-flash-lite, 2026-07-31
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This Mendelian randomization study found that genetically lower vitamin D levels are associated with increased risk of ovarian cancer in European women.
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.
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MeSH descriptors
Mendelian Randomization Analysis
Neoplasms, Glandular and Epithelial
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Ovarian Neoplasms
Polymorphism, Single Nucleotide
Vitamin D
Carcinoma, Ovarian Epithelial
Female
Genetic Predisposition to Disease
Humans
Neoplasms, Glandular and Epithelial
Neoplasms, Glandular and Epithelial
Odds Ratio
Ovarian Neoplasms
Ovarian Neoplasms
Risk Factors
Vitamin D
Vitamin D
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- europepmc
- last seen: 2026-10-18T09:30:06.152893+00:00
- pubmed
- last seen: 2026-10-08T21:18:26.654515+00:00
- unpaywall
- last seen: 2026-10-24T06:30:43.844863+00:00