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Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study.

Publication ,  Journal Article
Jiang, X; Dimou, NL; Al-Dabhani, K; Lewis, SJ; Martin, RM; Haycock, PC; Gunter, MJ; Key, TJ; Eeles, RA; Muir, K; Neal, D; Giles, GG; Zheng, W ...
Published in: Int J Epidemiol
October 1, 2019

BACKGROUND: Observational studies have suggested an association between circulating vitamin D concentrations [25(OH)D] and risk of breast and prostate cancer, which was not supported by a recent Mendelian randomization (MR) analysis comprising 15 748 breast and 22 898 prostate-cancer cases. Demonstrating causality has proven challenging and one common limitation of MR studies is insufficient power. METHODS: We aimed to determine whether circulating concentrations of vitamin D are causally associated with the risk of breast and prostate cancer, by using summary-level data from the largest ever genome-wide association studies conducted on vitamin D (N = 73 699), breast cancer (Ncase = 122 977) and prostate cancer (Ncase = 79 148). We constructed a stronger instrument using six common genetic variants (compared with the previous four variants) and applied several two-sample MR methods. RESULTS: We found no evidence to support a causal association between 25(OH)D and risk of breast cancer [OR per 25 nmol/L increase, 1.02 (95% confidence interval: 0.97-1.08), P = 0.47], oestrogen receptor (ER)+ [1.00 (0.94-1.07), P = 0.99] or ER- [1.02 (0.90-1.16), P = 0.75] subsets, prostate cancer [1.00 (0.93-1.07), P = 0.99] or the advanced subtype [1.02 (0.90-1.16), P = 0.72] using the inverse-variance-weighted method. Sensitivity analyses did not reveal any sign of directional pleiotropy. CONCLUSIONS: Despite its almost five-fold augmented sample size and substantially improved statistical power, our MR analysis does not support a causal effect of circulating 25(OH)D concentrations on breast- or prostate-cancer risk. However, we can still not exclude a modest or non-linear effect of vitamin D. Future studies may be designed to understand the effect of vitamin D in subpopulations with a profound deficiency.

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Published In

Int J Epidemiol

DOI

EISSN

1464-3685

Publication Date

October 1, 2019

Volume

48

Issue

5

Start / End Page

1416 / 1424

Location

England

Related Subject Headings

  • Vitamin D
  • Risk Factors
  • Receptors, Estrogen
  • Prostatic Neoplasms
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Mendelian Randomization Analysis
  • Male
  • Humans
  • Genome-Wide Association Study
 

Citation

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Jiang, X., Dimou, N. L., Al-Dabhani, K., Lewis, S. J., Martin, R. M., Haycock, P. C., … PRACTICAL, CRUK, BPC3, CAPS and PEGASUS consortia, . (2019). Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study. Int J Epidemiol, 48(5), 1416–1424. https://doi.org/10.1093/ije/dyy284
Jiang, Xia, Niki L. Dimou, Kawthar Al-Dabhani, Sarah J. Lewis, Richard M. Martin, Philip C. Haycock, Marc J. Gunter, et al. “Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study.Int J Epidemiol 48, no. 5 (October 1, 2019): 1416–24. https://doi.org/10.1093/ije/dyy284.
Jiang X, Dimou NL, Al-Dabhani K, Lewis SJ, Martin RM, Haycock PC, et al. Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study. Int J Epidemiol. 2019 Oct 1;48(5):1416–24.
Jiang, Xia, et al. “Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study.Int J Epidemiol, vol. 48, no. 5, Oct. 2019, pp. 1416–24. Pubmed, doi:10.1093/ije/dyy284.
Jiang X, Dimou NL, Al-Dabhani K, Lewis SJ, Martin RM, Haycock PC, Gunter MJ, Key TJ, Eeles RA, Muir K, Neal D, Giles GG, Giovannucci EL, Stampfer M, Pierce BL, Schildkraut JM, Warren Andersen S, Thompson D, Zheng W, Kraft P, Tsilidis KK, PRACTICAL, CRUK, BPC3, CAPS and PEGASUS consortia. Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study. Int J Epidemiol. 2019 Oct 1;48(5):1416–1424.
Journal cover image

Published In

Int J Epidemiol

DOI

EISSN

1464-3685

Publication Date

October 1, 2019

Volume

48

Issue

5

Start / End Page

1416 / 1424

Location

England

Related Subject Headings

  • Vitamin D
  • Risk Factors
  • Receptors, Estrogen
  • Prostatic Neoplasms
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Mendelian Randomization Analysis
  • Male
  • Humans
  • Genome-Wide Association Study