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

Authors:
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 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 Meir Stampfer Stacey Missmer Line Bjorge Helga B Salvesen Reidun K Kopperud Katharina Bischof Katja Kh Aben Lambertus A Kiemeney Leon Fag Massuger Angela Brooks-Wilson Sara H Olson Valerie McGuire Joseph H Rothstein Weiva Sieh Alice S Whittemore Linda S Cook Nhu D Le C Blake Gilks Jacek Gronwald Anna Jakubowska Jan Lubiński Tomasz Kluz Honglin Song Jonathan P Tyrer Nicolas Wentzensen Louise Brinton Britton Trabert Jolanta Lissowska John R McLaughlin Steven A Narod Catherine Phelan Hoda Anton-Culver Argyrios Ziogas Diana Eccles Ian Campbell Simon A Gayther Aleksandra Gentry-Maharaj Usha Menon Susan J Ramus Anna H Wu Agnieszka Dansonka-Mieszkowska Jolanta Kupryjanczyk Agnieszka Timorek Lukasz Szafron Julie M Cunningham Brooke L Fridley Stacey J Winham Elisa V Bandera Elizabeth M Poole Terry K Morgan Harvey A Risch Ellen L Goode Joellen M Schildkraut Celeste L Pearce Andrew Berchuck Paul Dp Pharoah Georgia Chenevix-Trench Puya Gharahkhani Rachel E Neale Penelope M Webb Stuart MacGregor

Int J Epidemiol 2016 10 4;45(5):1619-1630. Epub 2016 Sep 4.

Statistical Genetics laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia,

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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Source
http://dx.doi.org/10.1093/ije/dyw207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100621PMC
October 2016
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