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. 2023 Nov;149(17):15457-15467.
doi: 10.1007/s00432-023-05322-9. Epub 2023 Aug 29.

Circulating vitamin D concentration and risk of 14 cancers: a bidirectional Mendelian randomization study

Yuxuan Dai #  1 , Yu Chen #  2 , Yifu Pu  3 , Rui Jiang  4
Affiliations

Circulating vitamin D concentration and risk of 14 cancers: a bidirectional Mendelian randomization study

Yuxuan Dai et al. J Cancer Res Clin Oncol. 2023 Nov.

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.

Keywords: Cancer; Colorectal cancer; Melanoma skin cancer; Mendelian randomization; Vitamin D.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Bidirectional Mendelian randomized study design between circulating 25(OH)D concentrations and different types of cancer
Fig. 2
Fig. 2
Mendelian randomization results plot of circulating 25(OH) D concentrations and melanoma skin cancer (i). a Leave-one-out plot; b Scatter plot; c Funnel plot; d Forest plot
Fig. 3
Fig. 3
Mendelian randomization results plot of colorectal cancer and circulating 25(OH) D concentrations. a Leave-one-out plot; b scatter plot; c funnel plot; d forest plot
See this image and copyright information in PMC

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