Early Birds and Thyroid Cancer: Unveiling the Link Between Morningness and Thyroid Cancer Risk Through Mendelian Randomization.

BACKGROUND

The incidence of thyroid cancer (TC) has been rising globally, prompting concerns over potential risk factors. Morningness, a dimension of circadian preference, has been implicated in various health outcomes, including cancer risk. Our objective is to establish and implement a comprehensive Mendelian randomization (MR) framework aimed at investigating the relationship between sleep characteristics and thyroid cancer while also assessing its methodological challenges and implications for the design of clinical research.

METHODS

Single nucleotide polymorphisms (SNPs) associated with morningness was extracted from large-scale genome-wide association studies (GWAS). These SNPs were used to estimate the causal effect of morningness as instrumental variables on TC risk. We employed MR analysis using weighted median estimation (WM), inverse variance weighting (IVW), and MR-Egger regression. Sensitivity analyses, horizontal pleiotropy, and heterogeneity analyses were conducted to verify the robustness of the outcomes.

RESULTS

The MR-Egger regression analysis indicated a limited association between morningness and TC risk (odds ratio [OR] = 1.02, 95% confidence interval [CI]: 0.72-1.31, p = 0.98). However, the WM estimation suggested a slightly positive association (OR = 1.56, 95%CI: 0.72-2.28, p = 0.30), while the IVW method revealed a significant positive association (OR = 1.81, 95%CI: 1.01-3.24, p = 0.04). Pleiotropy analysis showed minimal influence, with the MR-Egger intercept not significant (p > 0.05). Heterogeneity analysis using Cochran's Q test indicated no significant heterogeneity (p > 0.05), supporting the consistency of the observed effect.

CONCLUSIONS

Our MR analysis suggests a potential positive association between morningness and the risk of thyroid cancer. The significant association observed with the IVW method suggests a possible association between morningness and TC risk; however, this finding should be interpreted with caution because the other MR methods did not show significant results. Further research is required to clarify the biological mechanisms underlying this association and to validate these findings in diverse populations.