Evaluating the Relationship between Cathepsins and Papillary Thyroid Carcinoma: A Mendelian Randomization Study

Area of Science:

• Genetics
• Oncology
• Biochemistry

Background:

• Papillary Thyroid Carcinoma (PTC) is the most prevalent thyroid malignancy.
• The precise etiology and progression of PTC remain incompletely understood.
• A potential link between cathepsins and PTC exists, but its causal nature requires investigation.

Purpose of the Study:

• To investigate the potential causal influence of cathepsins on the risk of developing papillary thyroid carcinoma.
• To utilize Mendelian Randomization (MR) to explore this genetic association.

Main Methods:

• Employed univariable and multivariable Mendelian Randomization (MR) analyses.
• Utilized genetic variants as instrumental variables for cathepsin levels.
• Sourced cathepsin genetic data from the INTERVAL study and PTC data from the Finnish Genome-Wide Association Study.

Main Results:

• MR analyses indicated a significant causal association between higher cathepsin levels and increased PTC risk.
• Genetic variants associated with higher cathepsin Z expression showed a positive causal link with PTC risk (OR: 1.1190).
• Multivariable analysis confirmed cathepsin Z's significant role in PTC carcinogenesis (OR: 1.1593).

Conclusions:

• Established a causal relationship between cathepsin levels and PTC risk.
• Highlighted the specific role of cathepsin Z in PTC progression.
• Suggests potential for novel therapeutic strategies targeting cathepsin enzymes in PTC treatment.