The relationship between cathepsins and nasopharyngeal carcinoma: a Mendelian randomization analysis

Observational studies have shown the potential for cathepsins (CTS) to have an effect on nasopharyngeal carcinoma (NPC), but their conclusions are susceptible to confounding factors.

To investigate the causal relationship between CTS and NPC, Mendelian randomization (MR) was conducted. Genetic data for nine CTS (CTS B, E, F, G, H, L2, O, S and Z) was obtained from a genome-wide association study. As the data on outcome, genetic data of NPC was utilized from a FinnGen study. MR was performed using five analytical methods including Inverse Variance-Weighted (IVW) method, MR-Egger test, Weighted Median test, Simple Mode test and Weighted Mode test, with the IVW as the main analysis method. Cochran's Q test, MR-PRESSO global test and "leave-one-out" sensitivity test were used in sensitivity analysis. Reverse MR was performed to investigate whether there is reverse causality between NPC and CTS. MR Steiger test was used to determine the direction of the interaction between CTS and NPC.

Overall, the authors found favorable evidence to support the association between Cathepsin F (CTSF) and NPC. CTSF was associated to increase the risk of NPC (odds ratio [OR] = 1.845, 95% confidence intervals [CI] = 1.086 ~ 3.136, P = 0.024) according to IVW. The results proved to be stable and robust in the sensitivity analysis. In the Steiger test, the causal effect of CTS on NPC was shown to be unidirectional.

These findings suggest that CTSF may plays an important role in NPC thus providing new research ideas for future basic research endeavors and clinical applications.