期刊
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
卷 45, 期 5, 页码 1619-1630出版社
OXFORD UNIV PRESS
DOI: 10.1093/ije/dyw207
关键词
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资金
- COGS project
- European Commission's Seventh Framework Programme Grant [223175 HEALTH F2 2009-223175]
- Genetic Associations and Mechanisms in Oncology (GAME-ON)
- NCI Cancer Post-GWAS Initiative [U19-CA148112]
- Ovarian Cancer Association Consortium
- Ovarian Cancer Research Fund
- California Cancer Research Program [00-01389V-20170, N01-CN25403, 2II0200]
- Canadian Institutes of Health Research [MOP-86727]
- Cancer Australia
- Cancer Council Victoria
- Cancer Council Queensland
- Cancer Council New South Wales
- Cancer Council South Australia
- Cancer Council Tasmania
- Cancer Foundation of Western Australia
- Cancer Institute of New Jersey
- Cancer Research UK [C490/A6187, C490/A10119, C490/A10124]
- Danish Cancer Society [94-222-52]
- ELAN Program of the University of Erlangen-Nuremberg
- Eve Appeal
- Helsinki University Central Hospital Research Fund
- Helse Vest
- Norwegian Cancer Society
- Norwegian Research Council
- Nationaal Kankerplan of Belgium
- L & S Milken Foundation
- Polish Ministry of Science and Higher Education [4 PO5C 028 14, 2 PO5A 068 27]
- Roswell Park Cancer Institute Alliance Foundation
- US National Cancer Institute (Intramural research funds) [K07-CA095666, K07-CA80668, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC67001, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA072720, P30-CA15083, P30-CA008748, P50-CA159981, P50-CA105009, P50-CA136393, R01-CA149429, R01-CA014089, R01-CA016056]
- NIH/National Center for Research Resources/General Clinical Research Center [MO1-RR000056]
- US Army Medical Research and Material Command [DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-07-0449, W81XWH-10-1-02802]
- US Public Health Service [PSA-042205]
- National Health and Medical Research Council of Australia [199600, 400281]
- German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research [01GB 9401]
- State of Baden-Wurttemberg through Medical Faculty of the University of Ulm [P.685]
- German Cancer Research Center
- Minnesota Ovarian Cancer Alliance
- Mayo Foundation
- Fred C. and Katherine B. Andersen Foundation
- Lon V. Smith Foundation [LVS-39420]
- Oak Foundation
- OHSU Foundation
- Mermaid I project
- Rudolf-Bartling Foundation
- UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge
- Imperial College London
- University College Hospital 'Womens Health Theme'
- Royal Marsden Hospital
- Work Safe BC 14
- University of Queensland
- QIMR Berghofer Medical Research Institute
- NHMRC Early Career Fellowship
- National Health and Medical Research Council
- Australian Research Council Future Fellowship
- [R01-CA017054]
- [R01-CA049449]
- [R01-CA050385]
- [R01-CA054419]
- [R01-CA058598]
- [R01-CA058860]
- [R01-CA061107]
- [R01-CA061132]
- [R01-CA063678]
- [R01-CA063682]
- [R01-CA067262]
- [R01-CA071766]
- [R01-CA074850]
- [R01-CA080978]
- [R01-CA083918]
- [R01-CA087538]
- [R01-CA092044]
- [R01-CA095023]
- [R01-CA126841]
- [R01-CA136924]
- [R03-CA113148]
- [R03-CA115195]
- [U01CA069417]
- [U01-CA071966]
- [UM1-CA186107]
- [UM1-CA176726]
- [R01-CA122443]
- [R01-CA112523]
- [R01-CA114343]
- Cancer Research UK [16561] Funding Source: researchfish
- Cancer Research UK
- The Francis Crick Institute [10124] Funding Source: researchfish
- Cancer Research UK
- The Francis Crick Institute [10119] Funding Source: researchfish
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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