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Cathepsins effect on diffuse large B cell lymphoma risk: A Mendelian randomization study.

Chuanyang Lu1,2,3, Qiuni Chen1,2,3, Yuye Shi1,2,3

  • 1Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu Province, China.

Medicine
|December 10, 2025
PubMed
Summary

This study found that elevated Cathepsin S (CTSS) levels causally increase the risk of diffuse large B cell lymphoma (DLBCL). Further research is needed to understand the mechanisms and develop new therapies for DLBCL patients.

Keywords:
Mendelian randomizationcathepsindiffuse large B cell lymphomainstrumental variantssingle nucleotide polymorphisms

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Area of Science:

  • Biochemistry
  • Oncology
  • Genetics

Background:

  • Cathepsins are increasingly linked to various diseases, including solid tumors and hematologic malignancies.
  • The causal relationship between cathepsins and malignant lymphomas remains unclear, necessitating further investigation.

Purpose of the Study:

  • To investigate the potential causal effect of cathepsins on the risk of developing malignant lymphomas using a Mendelian randomization approach.
  • Specifically, to determine if Cathepsin S (CTSS) has a causal role in diffuse large B cell lymphoma (DLBCL).

Main Methods:

  • Utilized a 2-sample Mendelian randomization (MR) analysis employing genome-wide association studies (GWAS) datasets for cathepsins and lymphomas.
  • Screened single nucleotide polymorphisms (SNPs) for genome-wide significance and linkage disequilibrium.
  • Performed sensitivity analyses and backward MR to ensure the robustness and validity of the findings.

Main Results:

  • Genetically predicted elevated Cathepsin S (CTSS) levels showed a significant positive association with an increased risk of diffuse large B cell lymphoma (DLBCL).
  • Patients with higher CTSS levels demonstrated a 20.6% increased hazard of developing DLBCL.
  • No causal effect was established for other cathepsins, and no reverse causality between DLBCL and CTSS was detected.

Conclusions:

  • This study provides evidence for a causal effect of Cathepsin S (CTSS) on the development of diffuse large B cell lymphoma (DLBCL).
  • Further research is warranted to elucidate the underlying biological mechanisms and explore novel therapeutic strategies targeting CTSS for DLBCL treatment.