Abstract
Background
Observational studies have revealed relationships between circulating vitamin D concentrations and the risk of different types of cancer, although the potential causal relationship remains controversial. This study aims to investigate the presence of a causal relationship between circulating vitamin D concentrations and the risk of different types of cancer.
Methods
Summary statistics from corresponding genome-wide association studies (GWASs) were used to investigate the causal relationship between circulating vitamin D concentrations and the risk of 14 cancers. A two-sample Mendelian randomization (MR) analysis using inverse-variance weighting (IVW) as the primary method was performed. Additionally, the results were verified using four other methods, including MR-Egger, weighted median, weighted mode, and simple mode. Multiple sensitivity analyses were conducted to ensure the robustness of our MR findings.
Results
The MR analysis showed no causal relationship between circulating vitamin D concentrations and most types of cancer, except for a causal relationship with melanoma skin cancer (MSC) (odds ratio [OR]IVW = 1.003, 95% confidence intervals [CI] 1.001–1.005, P = 0.004). Conversely, reverse MR revealed a causal relationship between circulating vitamin D concentration and colorectal cancer (ORIVW = 0.398, 95% CI 0.195–0.813, P = 0.01; ORweighted median = 0.352, 95% CI 0.135–0.917, P = 0.03).
Conclusions
Our findings provide support for a causal relationship between circulating vitamin D concentration and risk of MSC. Additionally, we found a causal relationship between circulating vitamin D concentration and risk of colorectal cancer in reverse-MR analysis. This evidence indicate that vitamin D is of great significance in the prevention and treatment of MSC and the prognosis of colorectal cancer.
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Availability of data and materials
This study was based on publicly available summarized data [IEU OPEN GWAS PROJECT: https://gwas.mrcieu.ac.uk/ (accessed on 1 June 2023)].
Abbreviations
- MR:
-
Mendelian randomization
- GWAS:
-
Genome-wide association study
- OR:
-
Odds ratio
- SNPs:
-
Single-nucleotide polymorphisms
- CI:
-
Confidence interval
- IVW:
-
Inverse-variance-weighted
- MR-PRESSO:
-
MR pleiotropy RESidual sum and outlier
- MSC:
-
Melanoma skin cancer
- NMSC:
-
Non-melanoma skin cancer
- NSNP:
-
Number of single-nucleotide polymorphism
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Acknowledgements
This work was made possible by the generous sharing of GWAS summary statistics. The authors would like to thank the participants, researchers, and staff associated with the many other studies from which we used data for this report. The authors would also like to thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript.
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DY and CY designed the study and drafted the paper. DY, CY, PY, and JR critically revised the paper. All authors read and approved the final manuscript.
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Additional file 1:
Table S1. The characteristics of SNPs adopted as instrumental variables of circulating 25(OH)D concentration. Table S2. Mendelian randomization results from different types of cancer to circulating 25(OH)D concentration. Table S3. The characteristics of SNPs adopted as instrumental variables of reverse Mendelian randomization. Table S4. Confounding factorsassociated with different types of cancer. Additional file 2: Figure S1. Leave-one-out inverse-variance weighted mendelian randomization analyses of circulating 25(OH)D concentration on different types of cancer. Figure S2. Scatter plot of the causal effect of circulating 25(OH)D concentration on different types of cancer. Figure S3. Funnel plot of the causal effect of circulating 25(OH)D concentration on different types of cancer. Figure S4. Forest plot of the causal effect of circulating 25(OH)D concentration on different types of cancer. Figure S5. Leave-one-out inverse-variance weighted mendelian randomization analyses of different types of cancer on circulating 25(OH)D concentration. Figure S6. Scatter plot of the causal effect of different types of cancer on circulating 25(OH)D concentration. Figure S7. Funnel plot of the causal effect of different types of cancer on circulating 25(OH)D concentration. Figure S8. Forest plot of the causal effect of different types of cancer on circulating 25(OH)D concentration. Figure S9. Mendelian randomization results plot of circulating 25(OH) D concentration and melanoma skin cancer (secondary validation). (RAR 4700 KB)
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Dai, Y., Chen, Y., Pu, Y. et al. Circulating vitamin D concentration and risk of 14 cancers: a bidirectional Mendelian randomization study. J Cancer Res Clin Oncol 149, 15457–15467 (2023). https://doi.org/10.1007/s00432-023-05322-9
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DOI: https://doi.org/10.1007/s00432-023-05322-9