Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Jiang X

PROVIDER: S-EPMC6934026 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Jiang Xia X Dimou Niki L NL Al-Dabhani Kawthar K Lewis Sarah J SJ Martin Richard M RM Haycock Philip C PC Gunter Marc J MJ Key Timothy J TJ Eeles Rosalind A RA Muir Kenneth K Neal David D Giles Graham G GG Giovannucci Edward L EL Stampfer Meir M Pierce Brandon L BL Schildkraut Joellen M JM Warren Andersen Shaneda S Thompson Deborah D Zheng Wei W Kraft Peter P Tsilidis Konstantinos K KK

International journal of epidemiology 20191001 5

<h4>Background</h4>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.<h4>Methods</h4>We aimed to determine whether circulating concentrations of vitamin D are ca ...[more]

PMID: 30597039

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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