Are cathepsins a risk factor for papillary thyroid carcinoma? A bidirectional two-sample mendelian randomization analysis

Background: Papillary thyroid carcinoma (PTC) is the most common type of endocrine tumor, and its incidence is on the rise. Observational studies have linked cathepsins, an endolysosomal cysteine protein hydrolase, to the malignant progression of several tumors, including PTC. However, the causal relationship between cathepsins and PTC remains unclear. The purpose of this study was to investigate the causal relationship between cathepsins and PTC using a bidirectional two-sample Mendelian randomization (MR) analysis.

Methods: Publicly available databases were used to obtain data on cathepsins and PTCs. Single nucleotide polymorphisms were screened for instrumental variables. Causality was evaluated using five methods. Heterogeneity and sensitivity analyses were performed to evaluate the stability of the results.

Results: The analysis revealed a significant association between cathepsin Z (CTSZ) and the risk of PTC (IVW, OR = 1.170, 95% CI: 1.035-1.102, P = 0.011). However, no association was found in the inverse analysis (IVW, OR = 1.006, 95% CI: 0.982-1.031, P = 0.612). The stability and reliability of the results of this study were indicated by both heterogeneity and sensitivity.

Conclusions: This study confirmed the association between CTSZ and an increased risk of PTC. This finding has important implications for clinical practice, as it may help to predict and screen for PTC at an early stage, as well as provide some guidance for therapeutic strategies against CTSZ.