TY - JOUR

T1 - Association of vitamin D levels and risk of ovarian cancer

T2 - a Mendelian randomization study

AU - Ong, Jue-Sheng

AU - Cuellar-Partida, Gabriel

AU - Lu, Yi

AU - Ovarian Cancer Study, Australian

AU - Fasching, Peter A

AU - Hein, Alexander

AU - Burghaus, Stefanie

AU - Beckmann, Matthias W

AU - Lambrechts, Diether

AU - Van Nieuwenhuysen, Els

AU - Vergote, Ignace

AU - Vanderstichele, Adriaan

AU - Anne Doherty, Jennifer

AU - Anne Rossing, Mary

AU - Chang-Claude, Jenny

AU - Eilber, Ursula

AU - Rudolph, Anja

AU - Wang-Gohrke, Shan

AU - Goodman, Marc T

AU - Bogdanova, Natalia

AU - Dörk, Thilo

AU - Dürst, Matthias

AU - Hillemanns, Peter

AU - Runnebaum, Ingo B

AU - Antonenkova, Natalia

AU - Butzow, Ralf

AU - Leminen, Arto

AU - Nevanlinna, Heli

AU - Pelttari, Liisa M

AU - Edwards, Robert P

AU - Kelley, Joseph L

AU - Modugno, Francesmary

AU - Moysich, Kirsten B

AU - Ness, Roberta B

AU - Cannioto, Rikki

AU - Høgdall, Estrid

AU - Høgdall, Claus K

AU - Jensen, Allan

AU - Giles, Graham G

AU - Bruinsma, Fiona

AU - Kjaer, Susanne K

AU - Hildebrandt, Michelle At

AU - Liang, Dong

AU - Lu, Karen H

AU - Wu, Xifeng

AU - Bisogna, Maria

AU - Dao, Fanny

AU - Levine, Douglas A

AU - Cramer, Daniel W

AU - Terry, Kathryn L

AU - Tworoger, Shelley S

AU - Stampfer, Meir

AU - Missmer, Stacey

AU - Bjorge, Line

AU - Salvesen, Helga B

AU - Kopperud, Reidun K

AU - Bischof, Katharina

AU - Aben, Katja Kh

AU - Kiemeney, Lambertus A

AU - Massuger, Leon Fag

AU - Brooks-Wilson, Angela

AU - Olson, Sara H

AU - McGuire, Valerie

AU - Rothstein, Joseph H

AU - Sieh, Weiva

AU - Whittemore, Alice S

AU - Cook, Linda S

AU - Le, Nhu D

AU - Blake Gilks, C

AU - Gronwald, Jacek

AU - Jakubowska, Anna

AU - Lubiński, Jan

AU - Kluz, Tomasz

AU - Song, Honglin

AU - Tyrer, Jonathan P

AU - Wentzensen, Nicolas

AU - Brinton, Louise

AU - Trabert, Britton

AU - Lissowska, Jolanta

AU - McLaughlin, John R

AU - Narod, Steven A

AU - Phelan, Catherine

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Eccles, Diana

AU - Campbell, Ian

AU - Gayther, Simon A

AU - Gentry-Maharaj, Aleksandra

AU - Menon, Usha

AU - Ramus, Susan J

AU - Wu, Anna H

AU - Dansonka-Mieszkowska, Agnieszka

AU - Kupryjanczyk, Jolanta

AU - Timorek, Agnieszka

AU - Szafron, Lukasz

AU - Cunningham, Julie M

AU - Fridley, Brooke L

AU - Winham, Stacey J

AU - Bandera, Elisa V

AU - Poole, Elizabeth M

AU - Morgan, Terry K

AU - Risch, Harvey A

AU - Goode, Ellen L

AU - Schildkraut, Joellen M

AU - Pearce, Celeste L

AU - Berchuck, Andrew

AU - Pharoah, Paul Dp

AU - Chenevix-Trench, Georgia

AU - Gharahkhani, Puya

AU - Neale, Rachel E

AU - Webb, Penelope M

AU - MacGregor, Stuart

N1 - © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

PY - 2016/10

Y1 - 2016/10

N2 - 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.

AB - 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.

U2 - 10.1093/ije/dyw207

DO - 10.1093/ije/dyw207

M3 - Journal article

C2 - 27594614

VL - 45

SP - 1619

EP - 1630

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

SN - 0300-5771

IS - 5

ER -