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

Australian Ovarian Cancer Study

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1619-1630
Number of pages12
JournalInternational Journal of Epidemiology
Volume45
Issue number5
DOIs
StatePublished - Jan 1 2016

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Random Allocation
Vitamin D
Ovarian Neoplasms
Observational Studies
Single Nucleotide Polymorphism
Odds Ratio
Epidemiologic Studies
Confidence Intervals
Neoplasms

ASJC Scopus subject areas

  • Epidemiology

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Association of vitamin D levels and risk of ovarian cancer : A Mendelian randomization study. / Australian Ovarian Cancer Study.

In: International Journal of Epidemiology, Vol. 45, No. 5, 01.01.2016, p. 1619-1630.

Research output: Contribution to journalArticle

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title = "Association of vitamin D levels and risk of ovarian cancer: A Mendelian randomization study",
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.",
author = "{Australian Ovarian Cancer Study} and Ong, {Jue Sheng} and Gabriel Cuellar-Partida and Yi Lu and Fasching, {Peter A.} and Alexander Hein and Stefanie Burghaus and Beckmann, {Matthias W.} and Diether Lambrechts and {Van Nieuwenhuysen}, Els and Ignace Vergote and Adriaan Vanderstichele and Doherty, {Jennifer Anne} and Rossing, {Mary Anne} and Jenny Chang-Claude and Ursula Eilber and Anja Rudolph and Shan Wang-Gohrke and Goodman, {Marc T.} and Natalia Bogdanova and Thilo D{\"o}rk and Matthias D{\"u}rst and Peter Hillemanns and Runnebaum, {Ingo B.} and Natalia Antonenkova and Ralf Butzow and Arto Leminen and Heli Nevanlinna and Pelttari, {Liisa M.} and Edwards, {Robert P.} and Kelley, {Joseph L.} and Francesmary Modugno and Moysich, {Kirsten B.} and Ness, {Roberta B.} and Rikki Cannioto and Estrid H{\o}gdall and H{\o}gdall, {Claus K.} and Allan Jensen and Giles, {Graham G.} and Fiona Bruinsma and Kjaer, {Susanne K.} and Hildebrandt, {Michelle A.T.} and Dong Liang and Lu, {Karen H.} and Xifeng Wu and Maria Bisogna and Fanny Dao and Levine, {Douglas A.} and Cramer, {Daniel W.} and Terry, {Kathryn L.} and Terry Morgan",
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TY - JOUR

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

T2 - A Mendelian randomization study

AU - Australian Ovarian Cancer Study

AU - Ong, Jue Sheng

AU - Cuellar-Partida, Gabriel

AU - Lu, Yi

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 - Doherty, Jennifer Anne

AU - Rossing, Mary Anne

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 A.T.

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 - Morgan, Terry

PY - 2016/1/1

Y1 - 2016/1/1

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.

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U2 - 10.1093/ije/dyw207

DO - 10.1093/ije/dyw207

M3 - Article

C2 - 27594614

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VL - 45

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EP - 1630

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

SN - 0300-5771

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