Vitamin D and risk of thyroid cancer: a two-sample Mendelian randomization study.

Objective: To investigate the causal effect of serum 25-hydroxyvitamin D (25(OH)D) on the risk of thyroid cancer (TC) by a two-sample Mendelian randomization (MR) analysis.

Methods: We analyzed data from two genome-wide association studies (GWAS), including 25(OH)D concentration levels in 417,580 individuals and 1415 individuals for TC. Genetic variants associated with serum 25(OH)D were selected as instrumental variables (IVs). The inverse-variance weighted (IVW) method served as the primary approach of MR analysis was used to evaluate the sensitivity of 25(OH)D to TC risk, while the weighted-median method, MR-Egger method, weighted mode and simple mode were employed as supplementary analyses. Cochran's Q test was used to test IV heterogeneity, MR-Egger regression test and MR-PRESSO global test were used to determine IV pleiotropy, and Leave-one-out analysis was used to check the stability of the results.

Results: 112 SNPs associated with serum 25(OH)D were identified as IVs. The IVW method showed a causal relationship between 25(OH)D and TC risk (OR = 0.761, 95% CI 0.584-0.991, P = 0.043). The results of the weighted-median method (OR = 0.858, 95%CI 0.606-1.216, P = 0.389), MR-Egger method (OR = 0.782, 95% CI 0.552-1.108, P = 0.169), weighted mode (OR = 0.779, 95%CI 0.568-1.068, P = 0.123) and simple mode (OR = 0.616, 95% CI 0.218-1.739, P = 0.362) enhance the credibility of the IVW results. Cochran's Q test, MR-Egger regression test and MR-PRESSO global test suggest that there is no significant heterogeneity and pleiotropy in IV. The leave-one-out analysis indicates that the results are stable.

Conclusion: There is a causal relationship between circulating vitamin D concentration and TC risk in the population. The lower the vitamin D levels, the higher the TC risk.