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

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.

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.

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 (OR_IVW = 0.398, 95% CI 0.195-0.813, P = 0.01; OR_{weighted median} = 0.352, 95% CI 0.135-0.917, P = 0.03).

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.