The causal relationship between cathepsins and digestive system tumors: a Mendelian randomization study

Area of Science:

• Genetics
• Oncology
• Gastroenterology

Background:

• Cathepsins play a known role in digestive system tumor development.
• Causal relationships between specific cathepsins and digestive cancers require further elucidation.

Purpose of the Study:

• To assess causal associations between nine cathepsins and six digestive system tumors using a bidirectional Mendelian randomization approach.
• To provide insights into potential diagnostic and therapeutic targets for digestive cancers.

Main Methods:

• A two-sample bidirectional Mendelian randomization study was performed.
• Genome-wide association study (GWAS) data for nine cathepsins and six digestive system tumors (HCC, PCa, BTC, CRC, GC, EC) were utilized.
• Standard MR analyses (IVW, MR-Egger, WM) and sensitivity analyses (Cochran's Q, MR-PRESSO, intercept test, leave-one-out) were employed.

Main Results:

• Increased cathepsin G levels were associated with higher risk of hepatocellular carcinoma (HCC).
• Elevated cathepsin B levels correlated with increased risk of biliary tract cancer (BTC).
• Higher cathepsin H levels were linked to a reduced risk of pancreatic cancer (PCa).
• Increased cathepsin L2 levels were associated with a lower risk of colorectal cancer (CRC).

Conclusions:

• This study confirms causal relationships between specific cathepsins and digestive system tumors.
• Findings offer valuable insights for the diagnosis and treatment of digestive system cancers.
• Cathepsins represent potential targets for novel therapeutic strategies in digestive oncology.