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Rigshospitalet - a part of Copenhagen University Hospital
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Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study

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  • Jue-Sheng Ong
  • Gabriel Cuellar-Partida
  • Yi Lu
  • Peter A Fasching
  • Alexander Hein
  • Stefanie Burghaus
  • Matthias W Beckmann
  • Diether Lambrechts
  • Els Van Nieuwenhuysen
  • Ignace Vergote
  • Adriaan Vanderstichele
  • Jennifer Anne Doherty
  • Mary Anne Rossing
  • Jenny Chang-Claude
  • Ursula Eilber
  • Anja Rudolph
  • Shan Wang-Gohrke
  • Marc T Goodman
  • Natalia Bogdanova
  • Thilo Dörk
  • Matthias Dürst
  • Peter Hillemanns
  • Ingo B Runnebaum
  • Natalia Antonenkova
  • Ralf Butzow
  • Arto Leminen
  • Heli Nevanlinna
  • Liisa M Pelttari
  • Robert P Edwards
  • Joseph L Kelley
  • Francesmary Modugno
  • Kirsten B Moysich
  • Roberta B Ness
  • Rikki Cannioto
  • Estrid Vilma Solyom Høgdall
  • Claus K Høgdall
  • Allan Jensen
  • Graham G Giles
  • Fiona Bruinsma
  • Susanne K Kjaer
  • Michelle At Hildebrandt
  • Dong Liang
  • Karen H Lu
  • Xifeng Wu
  • Maria Bisogna
  • Fanny Dao
  • Douglas A Levine
  • Daniel W Cramer
  • Kathryn L Terry
  • Shelley S Tworoger
  • Australian Ovarian Cancer Study
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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.

Original languageEnglish
JournalInternational Journal of Epidemiology
Volume45
Issue number5
Pages (from-to)1619-1630
Number of pages12
ISSN0300-5771
DOIs
Publication statusPublished - Oct 2016

ID: 49499872