Ovarian cancer risk increases 27 percent for each 8 ng lower level of Vitamin D – Sept 2016

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

Int J Epidemiol. 2016 Sep 4. pii: dyw207. [Epub ahead of print]

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Ong JS, Cuellar-Partida G, Lu Y, Ovarian Cancer Study A, 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, Blake Gilks C, 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 PD, Chenevix-Trench G, Gharahkhani P, Neale RE, Webb PM, MacGregor S.

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.

PMID: 27594614 DOI: 10.1093/ije/dyw207