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Circulating vitamin...
Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study
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- Jiang, X (author)
- Karolinska Institutet
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Dimou, NL (author)
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Al-Dabhani, K (author)
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Lewis, SJ (author)
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Martin, RM (author)
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Haycock, PC (author)
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Gunter, MJ (author)
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Key, TJ (author)
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Eeles, RA (author)
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Muir, K (author)
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Neal, D (author)
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Giles, GG (author)
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Giovannucci, EL (author)
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Stampfer, M (author)
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Pierce, BL (author)
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Schildkraut, JM (author)
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Andersen, SW (author)
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Thompson, D (author)
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Zheng, W (author)
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Kraft, P (author)
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Tsilidis, KK (author)
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(creator_code:org_t)
- 2018-12-28
- 2019
- English.
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In: International journal of epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 48:5, s. 1416-1424
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- BackgroundObservational 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.MethodsWe 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.ResultsWe 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.ConclusionsDespite 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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- By the author/editor
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Jiang, X
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Dimou, NL
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Al-Dabhani, K
-
Lewis, SJ
-
Martin, RM
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Haycock, PC
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show more...
-
Gunter, MJ
-
Key, TJ
-
Eeles, RA
-
Muir, K
-
Neal, D
-
Giles, GG
-
Giovannucci, EL
-
Stampfer, M
-
Pierce, BL
-
Schildkraut, JM
-
Andersen, SW
-
Thompson, D
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Zheng, W
-
Kraft, P
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Tsilidis, KK
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show less...
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Karolinska Institutet