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Association between stable angina pectoris and gastric cancer: two-sample bidirectional mendelian randomization study
Haoyu Zhao1, Xintong Ye1, Chuying Yu1
1Hangzhou TCM Hospital of Zhejiang Chinese Medical University (Hangzhou Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China.
Journal of Thrombosis and Thrombolysis
|April 25, 2025
Summary
This study investigated the causal link between stable angina pectoris (SAP) and gastric cancer (GC) using Mendelian randomization. Findings suggest SAP may reduce GC risk, but the reverse relationship requires further research.
Area of Science:
- Cardiovascular Epidemiology
- Gastrointestinal Oncology
- Genetic Epidemiology
Background:
- Stable angina pectoris (SAP) and gastric cancer (GC) share common risk factors and pathophysiological pathways, including oxidative stress.
- Existing epidemiological data suggest a potential inverse relationship between SAP and GC, but causal inference remains challenging.
Purpose of the Study:
- To investigate the potential bidirectional causal relationship between stable angina pectoris and gastric cancer using a robust Mendelian randomization approach.
- To assess whether genetic predisposition to SAP influences the risk of developing GC, and vice versa.
Main Methods:
- A two-sample bidirectional Mendelian randomization analysis was performed utilizing summary statistics from large genome-wide association studies (GWAS).
- Genetic variants associated with SAP and GC served as instrumental variables.
- Sensitivity analyses including MR-Egger intercept, MR-PRESSO, Cochran Q test, and leave-one-out methods were employed to assess pleiotropy and result robustness.
Main Results:
- Mendelian randomization analysis indicated a significant protective effect of stable angina pectoris on gastric cancer risk (OR=0.78, P=0.000027).
- Conversely, analysis with gastric cancer as the exposure showed a significant association with SAP (OR=0.87, P=0.024), but sensitivity analyses revealed potential pleiotropy, questioning the reliability of this direction.
- Robustness of the SAP-to-GC finding was supported by sensitivity analyses.
Conclusions:
- Genetic evidence suggests that stable angina pectoris may causally reduce the risk of gastric cancer.
- The potential causal effect of gastric cancer on stable angina pectoris is less certain due to evidence of pleiotropy.
- Further research is warranted to elucidate the complex interplay between these conditions, potentially involving oxidative stress pathways.
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