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

Author

Ong, Jue-Sheng, Dixon-Suen, Suzanne C., Han, Xikun, An, Jiyuan, Liyanage, Upekha, Dusingize, Jean-Cluade, Schumacher, Johannes, Gockel, Ines, Böhmer, Anne, Jankowski, Janusz, Palles, Claire, O’Mara, Tracy, Spurdle, Amanda, Law, Matthew H., Iles, Mark M., Pharoah, Paul, Berchuck, Andrew, Zheng, Wei, Thrift, Aaron P., Olsen, Catherine, Neale, Rachel E., Gharahkhani, Puya, Webb, Penelope M., MacGregor, Stuart, Fitzgerald, Rebecca, Buas, Matt, Gammon, Marilie D., Corley, Douglas A., Shaheen, Nicholas J., Hardie, Laura J., Bird, Nigel C., Reid, Brian J., Chow, Wong-Ho, Risch, Harvey A., Ye, Weimin, Liu, Geoffrey, Romero, Yvonne, Bernstein, Leslie, Wu, Anna H., Whiteman, David E., Vaughan, Thomas, Agee, M., Alipanahi, B., Auton, A., Bell, R. K., Bryc, K., Elson, S. L., Fontanillas, P., Furlotte, N. A., Hinds, D. A., Huber, K. E., Kleinman, A., Litterman, N. K., McIntyre, M. H., Mountain, J. L., Noblin, E. S., Northover, C. A. M., Pitts, S. J., Sathirapongsasuti, J. Fah, Sazonova, O. V., Shelton, J. F., Shringarpure, S., Tian, C., Tung, J. Y., Vacic, V., Wilson, C. H., Ong, Jue-Sheng [0000-0002-6062-710X], Dixon-Suen, Suzanne C. [0000-0003-3714-8386], Han, Xikun [0000-0002-3823-7308], Gockel, Ines [0000-0001-7423-713X], Böhmer, Anne [0000-0002-5716-786X], O’Mara, Tracy [0000-0002-5436-3232], Spurdle, Amanda [0000-0003-1337-7897], Law, Matthew H. [0000-0002-4303-8821], Iles, Mark M. [0000-0002-2603-6509], Pharoah, Paul [0000-0001-8494-732X], Zheng, Wei [0000-0003-1226-070X], Thrift, Aaron P. [0000-0002-0084-5308], Olsen, Catherine [0000-0003-4483-1888], Gharahkhani, Puya [0000-0002-4203-5952], Webb, Penelope M. [0000-0003-0733-5930], MacGregor, Stuart [0000-0001-6731-8142], and Apollo - University of Cambridge Repository

Subjects
631/67/68, 45/43, article, 692/699/67/2195, 692/4028/67/2324
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.

Published
2021
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2. A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

Author

Upekha E Liyanage, Amanda B. Spurdle, K. E. Huber, Anna H. Wu, J. Fah Sathirapongsasuti, Douglas A. Corley, C. Tian, Anne Böhmer, David A. Hinds, A. Auton, Xikun Han, Matt Buas, M. Agee, Rebecca C. Fitzgerald, Puya Gharahkhani, Yvonne Romero, S. L. Elson, Ines Gockel, Johannes Schumacher, Leslie Bernstein, Nigel C. Bird, Thomas L. Vaughan, E. S. Noblin, P. Fontanillas, Laura J. Hardie, Brian J. Reid, V. Vacic, M. H. McIntyre, Jiyuan An, Andrew Berchuck, Claire Palles, Weimin Ye, K. Bryc, S. J. Pitts, Jue-Sheng Ong, Geoffrey Liu, R. K. Bell, Rachel E. Neale, Marilie D. Gammon, J. L. Mountain, C. A. M. Northover, Catherine M. Olsen, C. H. Wilson, Janusz Jankowski, Matthew Law, A. Kleinman, Suzanne C. Dixon-Suen, J. Y. Tung, Aaron P. Thrift, Wong-Ho Chow, Paul Pharoah, Jean-Cluade Dusingize, Suyash Shringarpure, Mark M. Iles, Wei Zheng, N. A. Furlotte, Penelope M. Webb, B. Alipanahi, O. V. Sazonova, Stuart MacGregor, David Whiteman, J. F. Shelton, Harvey A. Risch, N. K. Litterman, Tracy A. O'Mara, Nicholas J. Shaheen, Ong, Jue-Sheng [0000-0002-6062-710X], Dixon-Suen, Suzanne C [0000-0003-3714-8386], Han, Xikun [0000-0002-3823-7308], Gockel, Ines [0000-0001-7423-713X], Böhmer, Anne [0000-0002-5716-786X], O'Mara, Tracy [0000-0002-5436-3232], Spurdle, Amanda [0000-0003-1337-7897], Law, Matthew H [0000-0002-4303-8821], Iles, Mark M [0000-0002-2603-6509], Pharoah, Paul [0000-0001-8494-732X], Zheng, Wei [0000-0003-1226-070X], Thrift, Aaron P [0000-0002-0084-5308], Olsen, Catherine [0000-0003-4483-1888], Gharahkhani, Puya [0000-0002-4203-5952], Webb, Penelope M [0000-0003-0733-5930], MacGregor, Stuart [0000-0001-6731-8142], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Science, General Physics and Astronomy, Sunburn, Single-nucleotide polymorphism, General Biochemistry, Genetics and Molecular Biology, Article, Cancer prevention, 03 medical and health sciences, 0302 clinical medicine, Cancer epidemiology, Risk Factors, Internal medicine, Neoplasms, Mendelian randomization, Vitamin D and neurology, medicine, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, Risk factor, Vitamin D, Child, Cancer genetics, Multidisciplinary, business.industry, Pigmentation, Case-control study, Cancer, Mendelian Randomization Analysis, General Chemistry, medicine.disease, Confidence interval, 030104 developmental biology, Case-Control Studies, Multivariate Analysis, business
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., Studies of the genetic association between vitamin D and cancer risk have typically been underpowered. Here the authors analyse this using Mendelian Randomisation with more than 70 vitamin D variants obtained from the UK Biobank and large-scale data from various consortia, confirming null associations between vitamin D and most cancers.

Published
2020

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