Malignant melanoma is a skin tumor with a poor prognosis. Therefore, it is critical to explore the risk factors associated with the outcome of this tumor. In the present study, Mendelian randomization (MR) was used to investigate the causal association between cathepsins and malignant melanoma. Summary statistical data on five cathepsins from European participants were extracted as exposure data. Data on melanoma from a genome‑wide association study of European ancestry were used as outcome data. Single nucleotide polymorphisms associated with cathepsins were used as instrumental variables (IVs). In a genome‑wide association study of malignant melanoma including 3,751 melanoma cases and 372,016 European ancestry controls, MR analysis was conducted to examine the effects of these IVs on melanoma. The inverse variance‑weighted method was used for MR analysis. In addition, MR‑Egger, weighted median and MR pleiotropy residual sum were used for complementary analyses. Furthermore, a series of sensitivity analyses were performed to ensure the validity and robustness of the results. The gene‑predicted results indicated no causal association between the five cathepsins and malignant melanoma (P>0.05). Cathepsin S [odds ratio (OR), 1.000; 95% confidence interval (CI), 0.999‑1.001; P=0.943], cathepsin B (OR, 1.000; 95% CI, 0.999‑1.001; P=0.763), cathepsin O (OR, 1.000; 95% CI, 0.999‑1.001; P=0.646), cathepsin E (OR, 0.999; 95% CI, 0.998‑1.001; P=0.375) and cathepsin L2 (OR, 1.101; 95% CI, 0.831‑1.458; P=0.503) were not significantly associated with the risk of developing melanoma. Sensitivity analysis demonstrated no significant bias in the aforementioned results. On the whole, in the present study, MR analysis did not provide evidence that cathepsins (cathepsin S, cathepsin B, cathepsin O, cathepsin E and cathepsin L2) are causally related to malignant melanoma.

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