Ong, JS;
Cuellar-Partida, G;
Lu, Y;
Ovarian Cancer Study, A;
Fasching, PA;
Hein, A;
Burghaus, S;
... MacGregor, S; + view all
(2016)
Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study.
International Journal of Epidemiology
, 45
(5)
pp. 1619-1630.
10.1093/ije/dyw207.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/ije/dyw207 |
| Publisher version: | http://doi.org/10.1093/ije/dyw207 |
| Language: | English |
| Additional information: | © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association. This is a pre-copyedited, author-produced PDF of an article accepted for publication in the International Journal of Epidemiology following peer review. The version of record Ong, JS; Cuellar-Partida, G; Lu, Y; Ovarian Cancer Study, A; Fasching, PA; Hein, A; Burghaus, S; (2016) Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study. International Journal of Epidemiology , 45 (5) pp. 1619-1630. 10.1093/ije/dyw207 is available online at: http://doi.org/10.1093/ije/dyw207 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1514794 |
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