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

Jue‐Sheng Ong, Gabriel Cuéllar-Partida, Lu Y, Fasching PA, Alexander Hein, Stefanie Burghaus, Beckmann MW, Diether Lambrechts, Van Nieuwenhuysen E, Vergote I, Adriaan Vanderstichele, Anne Doherty J, Anne Rossing M, Chang-Claude J, Eilber U, Rudolph A, Wang-Gohrke S, Marc T. Goodman, Natalia Bogdanova, Thilo Dörk, Dürst M, Peter Hillemanns, Runnebaum IB, Antonenkova N, Butzow R, Leminen A, Nevanlinna H, Liisa M. Pelttari, Edwards RP, Kelley JL, Modugno F, Moysich KB, Ness RB, Cannioto R, Høgdall E, Høgdall CK, Allan Jensen, Giles GG, Fiona Bruinsma, Kjaer SK, Hildebrandt MA, Dong Liang, Lu KH, Wu X, Bisogna M, Dao F, Douglas A. Levine, Cramer DW, Kathryn L. Terry, Shelley S. Tworoger, Stampfer M, Missmer S, Bjorge L, Salvesen HB, Kopperud RK, Bischof K, Katja K.H. Aben, Lambertus A. Kiemeney, Massuger LF, Brooks-Wilson A, Sara H. Olson, McGuire V, Rothstein JH, Weiva Sieh, Whittemore AS, Cook LS, Le ND, Gilks CB, Gronwald J, Anna Jakubowska, Jan Lubiński, Tomasz Kluz, Song H, Tyrer JP, Wentzensen N, Brinton L, Britton Trabert, Jolanta Lissowska, McLaughlin JR, Narod SA, Phelan C, Anton-Culver H, Ziogas A, Diana Eccles, Ian Campbell, Gayther SA, Gentry-Maharaj A, Usha Menon, Susan J. Ramus, Wu AH, Agnieszka Dansonka‐Mieszkowska, Jolanta Kupryjańczyk, Timorek A, Lukasz M. Szafron, Cunningham JM, Fridley BL, Stacey J. Winham, Bandera EV, Poole EM, Morgan TK, Risch HA, Goode EL, Schildkraut JM, Pearce CL, Berchuck A, Pharoah PD, Georgia Chenevix‐Trench, Gharahkhani P, Neale RE, Penelope M. Webb, Stuart MacGregor
International journal of epidemiology · 2016 · doi:10.1093/ije/dyw207 · PMID:27594614 · PMC5100621
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Abstract

BackgroundIn 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.MethodsWe 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).ResultsThe 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).ConclusionsGenetically 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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last seen: 2026-07-19T06:13:33.711413+00:00