Study on the causality of cathepsin on autoimmune diseases and cancer: evidence from mendelian randomization analysis

The genetic causality between cathepsin levels and autoimmune diseases (ADs) bidirectionally was investigated and the associated cancer risk was explored with Mendelian randomization. Mendelian randomization analyses were used to explore causal associations between cathepsin and 14 ADs. The final results came from a meta-analysis of two datasets to get a robust result. Furthermore, the potential carcinogenic effects of reduced cathepsin levels were explored. Sensitivity analyses were used to evaluate the robustness of the results. Based on the Mendelian randomization analysis, it was found that lower levels of specific cathepsins were associated with reduced risk of ADs. Reduced cathepsin E levels were linked to decreased susceptibility to psoriasis and a potential reduction in breast cancer risk. Reduced cathepsins G and L2 showed an inhibitory effect on psoriasis without increasing cancer risk. These results emphasized the genetic causal connection between cathepsin and ADs. Targeting cathepsins may be beneficial in treating ADs, but potential oncogenic effects must be considered to provide a basis for safer therapeutic strategies.