Association between stable angina pectoris and gastric cancer: two-sample bidirectional mendelian randomization study.

Abstract

To explore the possible causal link between stable angina pectoris (SAP) and gastric cancer (GC) through Mendelian randomization analysis. We used data from genome-wide association studies (GWAS) statistical datasets, with SAP and GC screened as relevant instrumental variables for exposure factors, respectively. To evaluate the causal link between SAP and GC, a two-sample bidirectional Mendelian randomization analysis was conducted, leveraging genetic variants as instrumental variables. In addition, effects of horizontal pleiotropy were evaluated using MR-PRESSO and MR-Egger intercept analysis. Sensitivity analysis was performed using Cochran Q test and "leave one out" method. The study showed a significant causal relationship between SAP and GC in the analysis with SAP as the exposure variable (odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.69-0.87, p = 0.000027 using inverse variance weighting [IVW]). Sensitivity analysis confirmed the robustness of Mendelian randomization results. In the analysis of GC as an exposure variable, gastric cancer and SAP also showed a significant causal association (OR = 0.87, 95%CI = 0.77-0.98, p = 0.024 using IVW), but sensitivity analysis suggested a significant pleiotropy between instrumental variables (p = 0.0093 using MR-Egger intercept analysis), which cast doubt on the reliability of the study and requires careful interpretation of the results. Existing studies suggest that individuals with SAP may have a lower risk of developing GC. However, the precise causal relationship, particularly regarding whether GC contributes to an increased risk of SAP, remains unclear and warrants further investigation. GC and ischemic heart disease which represented by SAP are both associated with oxidative stress in their pathogenesis. Local tissue-induced mitochondrial autophagy or cellular ferroptosis triggers a systemic response, potentially underlying the negative correlation between GC and SAP. Thus, therapeutic strategies that target the interplay between local tissue and systemic responses in oxidative stress may hold promise for the benefits to patients.