Chen Shubin, Ning Ruiling, Jiang Wei, Zhou Shaozhang, Yu Qitao, Gan Haijie
Medical Oncology of Respiratory, Guangxi Medical University Cancer Hospital, Nanning, China.
Front Med (Lausanne). 2024 Jul 8;11:1419612. doi: 10.3389/fmed.2024.1419612. eCollection 2024.
Observational studies suggest a connection between ACE2 (angiotensin-converting enzyme 2) and lung cancer. However, it's not apparent if confounding variables are interfering with the link. Therefore, we aimed to define the relationships between ACE2 and the risk of lung cancer.
With the aim of developing genetic tools, we selected SNPs substantially associated with ACE2 using a statistically significant criterion. The relevant SNPs were then taken from the lung cancer GWAS dataset for additional research. After that, we used two-sample Mendelian randomization (MR) to ascertain if ACE2 is causally linked to the risk of developing lung cancer. To investigate the causal links' directions, we also performed a reverse MR analysis.
According to our findings, there is strong evidence that ACE2 is linked to a decreased chance of developing lung cancer (odds ratio: 0.94; 95% confidence interval: 0.90-0.98; = 0.0016). The IVW method, the major MR analysis, was not impacted by heterogeneity in any of the analyses, according to Cochrane's Q test ( = 0.207). The MR-Egger intercept ( = 0.622) showed no indication of horizontal pleiotropy in any of the investigations. Outlier SNPs were not detected by the MR-PRESSO global test ( = 0.191). The leave-one-out analysis was performed, and the results showed a steady outcome. Nonsignificant causal estimates between lung cancer and ACE2 were produced by reverse MR analysis.
MR investigation revealed a significant causal link between ACE2 and the risk of getting lung cancer. These findings may have implications for public health measures aimed at reducing the incidence of lung cancer.
观察性研究表明血管紧张素转换酶2（ACE2）与肺癌之间存在联系。然而，尚不清楚是否有混杂变量干扰了这种联系。因此，我们旨在明确ACE2与肺癌风险之间的关系。
为了开发基因工具，我们使用具有统计学意义的标准选择了与ACE2显著相关的单核苷酸多态性（SNP）。然后从肺癌全基因组关联研究（GWAS）数据集中提取相关SNP进行进一步研究。之后，我们使用两样本孟德尔随机化（MR）来确定ACE2是否与患肺癌的风险存在因果关系。为了研究因果关系的方向，我们还进行了反向MR分析。
根据我们的研究结果，有强有力的证据表明ACE2与患肺癌几率降低有关（优势比：0.94；95%置信区间：0.90 - 0.98；P = 0.0016）。根据Cochrane's Q检验（P = 0.207），主要的MR分析方法——逆方差加权（IVW）法在任何分析中均未受到异质性的影响。MR-Egger截距（P = 0.622）在任何研究中均未显示出水平多效性的迹象。MR-PRESSO全局检验未检测到异常SNP（P = 0.191）。进行了留一法分析，结果显示结果稳定。反向MR分析得出肺癌与ACE2之间无显著因果估计值。
MR研究揭示了ACE2与患肺癌风险之间存在显著的因果关系。这些发现可能对旨在降低肺癌发病率的公共卫生措施具有启示意义。
