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Updated: Sep 16, 2025
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Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
Published on: September 20, 2024
545
Causal Associations Between Cystatin and Lung Cancer: A Two-Sample Mendelian Randomization Study
Chunling Zhang1, Riya Wu1, Hang Liu1
1Department of Pulmonary Disease, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
The Clinical Respiratory Journal
|July 11, 2025
Summary
Genetically predicted Cystatin 8 shows a causal link to squamous cell lung carcinoma. Further research is needed to confirm this association in population studies.
Area of Science:
- Genetics
- Oncology
- Biochemistry
Background:
- The cystatin family plays a role in lung cancer development, influencing inflammation and protease balance.
- Previous studies suggest associations between cystatins and lung cancer, but causal links remain unclear.
Purpose of the Study:
- To investigate the potential causal relationships between cystatins and lung cancer subtypes using Mendelian randomization.
- To determine if genetic variations in cystatins influence the risk of developing lung cancer.
Main Methods:
- A two-sample Mendelian randomization (MR) study was performed using genomic data for seven cystatins and three lung cancer subtypes.
- The inverse-variance weighted (IVW) method was the primary analysis, with weighted median, mode, and MR-Egger regression used for validation.
- Sensitivity analyses, including MR-Egger regression, Cochran's Q test, MR-PRESSO, and Radial MR, were employed to assess pleiotropy and handle outliers.
Main Results:
- Genetically predicted Cystatin 8 demonstrated a significant causal association with squamous cell lung carcinoma (OR = 1.062, p = 0.035).
- After outlier removal, Cystatin D showed a significant causal association with lung adenocarcinoma (OR = 1.178, p = 0.023).
- No significant causal relationships were found for other cystatins (B, D, F, M) with lung cancer subtypes before outlier adjustment.
Conclusions:
- Genetically predicted Cystatin 8 is causally associated with squamous cell lung carcinoma.
- Further population-based studies are necessary to validate these findings and explore the underlying mechanisms.
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