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

Ong, Jue-Sheng, Cuellar-Partida, Gabriel, Lu, Yi, Fasching, Peter A., Hein, Alexander, Burghaus, Stefanie, Beckmann, Matthias W., Lambrechts, Diether, Van Nieuwenhuysen, Els, Vergote, Ignace, Vanderstichele, Adriaan, Doherty, Jennifer Anne, Rossing, Mary Anne, Chang-Claude, Jenny, Eilber, Ursula, Rudolph, Anja, Wang-Gohrke, Shan, Goodman, Marc T., Bogdanova, Natalia, Dork, Thilo, Durst, Matthias, Hillemanns, Peter, Runnebaum, Ingo B., Antonenkova, Natalia, Butzow, Ralf, Leminen, Arto, Nevanlinna, Heli, Pelttari, Liisa M., Edwards, Robert P., Kelley, Joseph L., Modugno, Francesmary, Moysich, Kirsten B., Ness, Roberta B., Cannioto, Rikki, Hogdall, Estrid, Hogdall, Claus K., Jensen, Allan, Giles, Graham G., Bruinsma, Fiona, Kjaer, Susanne K., Hildebrandt, Michelle A. T., Liang, Dong, Lu, Karen H., Wu, Xifeng, Bisogna, Maria, Dao, Fanny, Levine, Douglas A., Cramer, Daniel W., Terry, Kathryn L., Tworoger, Shelley S., Stampfer, Meir, Missmer, Stacey, Bjorge, Line, Salvesen, Helga B., Kopperud, Reidun K., Bischof, Katharina, Aben, Katja K. H., Kiemeney, Lambertus A., Massuger, Leon F. A. G., Brooks-Wilson, Angela, Olson, Sara H., McGuire, Valerie, Rothstein, Joseph H., Sieh, Weiva, Whittemore, Alice S., Cook, Linda S., Le, Nhu D., Gilks, C. Blake, Gronwald, Jacek, Jakubowska, Anna, Lubinski, Jan, Kluz, Tomasz, Song, Honglin, Tyrer, Jonathan P., Wentzensen, Nicolas, Brinton, Louise, Trabert, Britton, Lissowska, Jolanta, McLaughlin, John R., Narod, Steven A., Phelan, Catherine, Anton-Culver, Hoda, Ziogas, Argyrios, Eccles, Diana, Campbell, Ian, Gayther, Simon A., Gentry-Maharaj, Aleksandra, Menon, Usha, Ramus, Susan J., Wu, Anna H., Dansonka-Mieszkowska, Agnieszka, Kupryjanczyk, Jolanta, Timorek, Agnieszka, Szafron, Lukasz, Cunningham, Julie M., Fridley, Brooke L., Winham, Stacey J., Bandera, Elisa V., Poole, Elizabeth M., Morgan, Terry K., Risch, Harvey A., Goode, Ellen L., Schildkraut, Joellen M., Pearce, Celeste L., Berchuck, Andrew, Pharoah, Paul D. P., Chenevix-Trench, Georgia, Gharahkhani, Puya, Neale, Rachel E., Webb, Penelope M. and MacGregor, Stuart (2016) Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study. International Journal of Epidemiology, 45 5: 1619-1630. doi:10.1093/ije/dyw207


Author Ong, Jue-Sheng
Cuellar-Partida, Gabriel
Lu, Yi
Fasching, Peter A.
Hein, Alexander
Burghaus, Stefanie
Beckmann, Matthias W.
Lambrechts, Diether
Van Nieuwenhuysen, Els
Vergote, Ignace
Vanderstichele, Adriaan
Doherty, Jennifer Anne
Rossing, Mary Anne
Chang-Claude, Jenny
Eilber, Ursula
Rudolph, Anja
Wang-Gohrke, Shan
Goodman, Marc T.
Bogdanova, Natalia
Dork, Thilo
Durst, Matthias
Hillemanns, Peter
Runnebaum, Ingo B.
Antonenkova, Natalia
Butzow, Ralf
Leminen, Arto
Nevanlinna, Heli
Pelttari, Liisa M.
Edwards, Robert P.
Kelley, Joseph L.
Modugno, Francesmary
Moysich, Kirsten B.
Ness, Roberta B.
Cannioto, Rikki
Hogdall, Estrid
Hogdall, Claus K.
Jensen, Allan
Giles, Graham G.
Bruinsma, Fiona
Kjaer, Susanne K.
Hildebrandt, Michelle A. T.
Liang, Dong
Lu, Karen H.
Wu, Xifeng
Bisogna, Maria
Dao, Fanny
Levine, Douglas A.
Cramer, Daniel W.
Terry, Kathryn L.
Tworoger, Shelley S.
Stampfer, Meir
Missmer, Stacey
Bjorge, Line
Salvesen, Helga B.
Kopperud, Reidun K.
Bischof, Katharina
Aben, Katja K. H.
Kiemeney, Lambertus A.
Massuger, Leon F. A. G.
Brooks-Wilson, Angela
Olson, Sara H.
McGuire, Valerie
Rothstein, Joseph H.
Sieh, Weiva
Whittemore, Alice S.
Cook, Linda S.
Le, Nhu D.
Gilks, C. Blake
Gronwald, Jacek
Jakubowska, Anna
Lubinski, Jan
Kluz, Tomasz
Song, Honglin
Tyrer, Jonathan P.
Wentzensen, Nicolas
Brinton, Louise
Trabert, Britton
Lissowska, Jolanta
McLaughlin, John R.
Narod, Steven A.
Phelan, Catherine
Anton-Culver, Hoda
Ziogas, Argyrios
Eccles, Diana
Campbell, Ian
Gayther, Simon A.
Gentry-Maharaj, Aleksandra
Menon, Usha
Ramus, Susan J.
Wu, Anna H.
Dansonka-Mieszkowska, Agnieszka
Kupryjanczyk, Jolanta
Timorek, Agnieszka
Szafron, Lukasz
Cunningham, Julie M.
Fridley, Brooke L.
Winham, Stacey J.
Bandera, Elisa V.
Poole, Elizabeth M.
Morgan, Terry K.
Risch, Harvey A.
Goode, Ellen L.
Schildkraut, Joellen M.
Pearce, Celeste L.
Berchuck, Andrew
Pharoah, Paul D. P.
Chenevix-Trench, Georgia
Gharahkhani, Puya
Neale, Rachel E.
Webb, Penelope M.
MacGregor, Stuart
Title Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study
Journal name International Journal of Epidemiology   Check publisher's open access policy
ISSN 0300-5771
1464-3685
Publication date 2016-10-01
Sub-type Article (original research)
DOI 10.1093/ije/dyw207
Open Access Status Not yet assessed
Volume 45
Issue 5
Start page 1619
End page 1630
Total pages 12
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Abstract 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.
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID P30 CA016672
P30 CA046592
P30 CA008748
10119
P50 CA136393
10124
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
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