A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

Esophageal Cancer Consortium; 23 and Me Research Team

doi:10.1038/s41467-020-20368-w

A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

Esophageal Cancer Consortium, 23 and Me Research Team

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.

Original language	English (US)
Article number	246
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20368-w
State	Published - Dec 1 2021
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-020-20368-w

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@article{df3ffe7384734f1093bc3009242c6d06,

title = "A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization",

abstract = "Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.",

author = "{Esophageal Cancer Consortium} and {23 and Me Research Team} and Ong, {Jue Sheng} and Dixon-Suen, {Suzanne C.} and Xikun Han and Jiyuan An and Rebecca Fitzgerald and Matt Buas and Gammon, {Marilie D.} and Corley, {Douglas A.} and Shaheen, {Nicholas J.} and Hardie, {Laura J.} and Bird, {Nigel C.} and Reid, {Brian J.} and Chow, {Wong Ho} and Risch, {Harvey A.} and Weimin Ye and Geoffrey Liu and Yvonne Romero and Leslie Bernstein and Wu, {Anna H.} and Whiteman, {David E.} and Thomas Vaughan and M. Agee and B. Alipanahi and A. Auton and Bell, {R. K.} and K. Bryc and Elson, {S. L.} and P. Fontanillas and Furlotte, {N. A.} and Hinds, {D. A.} and Huber, {K. E.} and A. Kleinman and Litterman, {N. K.} and McIntyre, {M. H.} and Mountain, {J. L.} and Noblin, {E. S.} and Northover, {C. A.M.} and Pitts, {S. J.} and Sathirapongsasuti, {J. Fah} and Sazonova, {O. V.} and Shelton, {J. F.} and S. Shringarpure and C. Tian and Tung, {J. Y.} and V. Vacic and Wilson, {C. H.} and Upekha Liyanage and Dusingize, {Jean Cluade} and Johannes Schumacher and Ines Gockel",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

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doi = "10.1038/s41467-020-20368-w",

language = "English (US)",

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T1 - A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

AU - Esophageal Cancer Consortium

AU - 23 and Me Research Team

AU - Ong, Jue Sheng

AU - Dixon-Suen, Suzanne C.

AU - Han, Xikun

AU - An, Jiyuan

AU - Fitzgerald, Rebecca

AU - Buas, Matt

AU - Gammon, Marilie D.

AU - Corley, Douglas A.

AU - Shaheen, Nicholas J.

AU - Hardie, Laura J.

AU - Bird, Nigel C.

AU - Reid, Brian J.

AU - Chow, Wong Ho

AU - Risch, Harvey A.

AU - Ye, Weimin

AU - Liu, Geoffrey

AU - Romero, Yvonne

AU - Bernstein, Leslie

AU - Wu, Anna H.

AU - Whiteman, David E.

AU - Vaughan, Thomas

AU - Agee, M.

AU - Alipanahi, B.

AU - Auton, A.

AU - Bell, R. K.

AU - Bryc, K.

AU - Elson, S. L.

AU - Fontanillas, P.

AU - Furlotte, N. A.

AU - Hinds, D. A.

AU - Huber, K. E.

AU - Kleinman, A.

AU - Litterman, N. K.

AU - McIntyre, M. H.

AU - Mountain, J. L.

AU - Noblin, E. S.

AU - Northover, C. A.M.

AU - Pitts, S. J.

AU - Sathirapongsasuti, J. Fah

AU - Sazonova, O. V.

AU - Shelton, J. F.

AU - Shringarpure, S.

AU - Tian, C.

AU - Tung, J. Y.

AU - Vacic, V.

AU - Wilson, C. H.

AU - Liyanage, Upekha

AU - Dusingize, Jean Cluade

AU - Schumacher, Johannes

AU - Gockel, Ines

PY - 2021/12/1

Y1 - 2021/12/1

N2 - Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.

AB - Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.

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JO - Nature communications

JF - Nature communications

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ER -

A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

Abstract

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