Zhao Haoyu, Ye Xintong, Yu Chuying, Huang Jie, Xu Tianxiang, Song Canyang, Liu Qingsheng
Hangzhou TCM Hospital of Zhejiang Chinese Medical University (Hangzhou Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China.
The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
J Thromb Thrombolysis. 2025 Apr 26. doi: 10.1007/s11239-025-03089-z.
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.
通过孟德尔随机化分析探索稳定型心绞痛（SAP）与胃癌（GC）之间可能的因果联系。我们使用了全基因组关联研究（GWAS）统计数据集的数据，分别将SAP和GC作为暴露因素的相关工具变量进行筛选。为了评估SAP与GC之间的因果联系，利用遗传变异作为工具变量进行了两样本双向孟德尔随机化分析。此外，使用MR-PRESSO和MR-Egger截距分析评估了水平多效性的影响。采用Cochran Q检验和“留一法”进行敏感性分析。研究显示，以SAP作为暴露变量的分析中，SAP与GC之间存在显著的因果关系（比值比[OR]=0.78，95%置信区间[CI]=0.69-0.87，采用逆方差加权[IVW]时p=0.000027）。敏感性分析证实了孟德尔随机化结果的稳健性。在以GC作为暴露变量的分析中，胃癌与SAP也显示出显著的因果关联（OR=0.87，95%CI=0.77-0.98，采用IVW时p=0.024），但敏感性分析表明工具变量之间存在显著的多效性（采用MR-Egger截距分析时p=0.0093），这对研究的可靠性提出了质疑，需要对结果进行谨慎解读。现有研究表明，患有SAP的个体患GC的风险可能较低。然而，确切的因果关系，特别是GC是否会增加SAP的风险，仍不清楚，值得进一步研究。以SAP为代表的GC和缺血性心脏病在发病机制上均与氧化应激相关。局部组织诱导的线粒体自噬或细胞铁死亡引发全身反应，这可能是GC与SAP之间负相关的潜在原因。因此，针对氧化应激中局部组织与全身反应相互作用的治疗策略可能有望给患者带来益处。
