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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ong, J-S; Cuellar-Partida, G; Lu, Y; Australian Ovarian Cancer Study, ; 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; Gilks, CB; Gronwald, J; Jakubowska, A; LubiƄski, 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

Published Date

  • October 2016

Published In

Volume / Issue

  • 45 / 5

Start / End Page

  • 1619 - 1630

PubMed ID

  • 27594614

Pubmed Central ID

  • 27594614

Electronic International Standard Serial Number (EISSN)

  • 1464-3685

Digital Object Identifier (DOI)

  • 10.1093/ije/dyw207

Language

  • eng

Conference Location

  • England