Do metabolic factors increase the risk of thyroid cancer? a Mendelian randomization study

BACKGROUND: Epidemiological studies emphasize the link between metabolic factors and thyroid cancer. Using Mendelian randomization (MR), we assessed the possible causal impact of metabolic factors on thyroid cancer for the first time. METHODS: Summary statistics for metabolic factors and thyroid cancer were obtained from published Genome-wide association studies. The causal relationships were assessed using the inverse-variance weighted (IVW) method as the primary method through a two-sample Mendelian Randomization (MR) analysis. To account for the potential existence of horizontal pleiotropy, four additional methods were employed, including Mendelian Randomization–Egger (MR-Egger), weighted median method (WM), simple mode, and weighted mode method. Given the presence of interactions between metabolic factors, a multivariable MR analysis was subsequently conducted. RESULTS: The results showed there was a genetic link between HDL level and protection effect of thyroid cancer using IVW (OR= 0.75, 95% confidence intervals [CIs] 0.60-0.93, p=0.01) and MR-Egger method (OR= 0.70, 95% confidence intervals [CIs] 0.50- 0.97, p=0.03). The results remained robust in multivariable MR analysis for the genetic link between HDL level and protection effect of thyroid cancer (OR= 0.74, 95% confidence intervals [CIs] 0.55-0.99, p=0.04). CONCLUSIONS: This study suggests a protection role for HDL on thyroid cancer. The study findings provide evidence for the public health suggestion for thyroid cancer prevention. HDL’s potential as a pharmacological target needs further validation.