The UVMR analyses discovered that elevated SNP-predicted cathepsin S expression were significantly associated with increased colorectal cancer risk(IVW: p = 0.0162, odds ratio (OR) = 1.0513, 95% confidence interval (CI) = 1.0093–1.0951), whereas cathepsin H exhibited a protective role against pancreatic cancer(IVW: p = 0.0410, OR = 0.9131, 95% CI = 0.8369–0.9963). Here, CTSH is linked to colorectal cancer.