Liao Zhicheng, Jia Pengcheng, Pang Liang, Chen Yirui, Zhang Jizhou
Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, Zhejiang Province, China.
Medicine (Baltimore). 2025 Jul 25;104(30):e43378. doi: 10.1097/MD.0000000000043378.
Many observational studies have demonstrated an association between coronary atherosclerosis (CAS) and lung cancer (LUCA). However, there is not enough evidence to justify a direct genetic causal effect between CAS and LUCA as well as its subtypes. This study aimed to use Mendelian randomization (MR) analysis to assess the causal relationship between CAS and LUCA as well as its subtypes at the genetic level. This study was designed following the STROBE-MR guidelines and was a bidirectional two-sample MR analysis based on the context of the European population. It extracted genome-wide association study (GWAS) data of 51,589 CAS patients from the FinnGen Biobank database and extracted GWAS data of patients with LUCA and its subtypes from the IEU open GWAS database for MR analysis. In addition, this study used heterogeneity tests, sensitivity analyses, and multiple validity analyses to ensure the accuracy and robustness of the results. In the forward MR results, there was a statistically significant difference between CAS and LUCA (odds ratio [OR]: 0.88, 95% confidence interval [95% CI]: 0.82-0.95, P = .00099), and in the subtype analysis, there was a statistically significant difference between CAS and lung squamous cell carcinoma (LUSC) (OR [95% CI]: 0.84 [0.75-0.94], P = .00322); there was no statistical significance between CAS and either lung adenocarcinoma or small cell LUCA (OR [95% CI]: 0.93 [0.84-1.03], P = .1426; OR [95% CI]: 0.87 [0.73-1.03], P = .1145). In the reverse MR results, there was no statistical significance between LUCA and CAS as well as between LUSC and CAS (OR [95% CI]: 0.96 [0.92-1.01], P = .099; OR [95% CI]: 1.03 [0.95-1.10], P = .382). The study results showed that CAS has a genetic causal effect on LUCA and its subtype LUSC and that the effect is protective. Further studies are required to explore the underlying mechanisms.
许多观察性研究已证明冠状动脉粥样硬化（CAS）与肺癌（LUCA）之间存在关联。然而，尚无足够证据证明CAS与LUCA及其亚型之间存在直接的遗传因果效应。本研究旨在使用孟德尔随机化（MR）分析在基因水平评估CAS与LUCA及其亚型之间的因果关系。本研究遵循STROBE-MR指南设计，是基于欧洲人群背景的双向两样本MR分析。它从芬兰基因生物银行数据库中提取了51589例CAS患者的全基因组关联研究（GWAS）数据，并从IEU开放GWAS数据库中提取了LUCA及其亚型患者的GWAS数据用于MR分析。此外，本研究使用了异质性检验、敏感性分析和多种有效性分析来确保结果的准确性和稳健性。在前向MR结果中，CAS与LUCA之间存在统计学显著差异（优势比[OR]：0.88，95%置信区间[95%CI]：0.82 - 0.95，P = 0.00099），在亚型分析中，CAS与肺鳞状细胞癌（LUSC）之间存在统计学显著差异（OR[95%CI]：0.84[0.75 - 0.94]，P = 0.00322）；CAS与肺腺癌或小细胞LUCA之间无统计学显著差异（OR[95%CI]：0.93[0.84 - 1.03]，P = 0.1426；OR[95%CI]：0.87[0.73 - 1.03]，P = 0.1145）。在反向MR结果中，LUCA与CAS之间以及LUSC与CAS之间无统计学显著差异（OR[95%CI]：0.96[0.92 - 1.01]，P = 0.099；OR[95%CI]：1.03[0.95 - 1.10]，P = 0.382）。研究结果表明，CAS对LUCA及其亚型LUSC具有遗传因果效应，且该效应具有保护作用。需要进一步研究以探索其潜在机制。
