He Dongming, Lu Hongting, Ou Xinhuai, Zheng Tiaozhan, Zheng Zhiwen, Xu Zhanyu, Duan Xiaohong, Li Shikang
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, P. R. China.
Guangxi Minzu University, Guangxi Zhuang Autonomous Region, Nanning, 530006, P. R. China.
BMC Cancer. 2025 Jan 27;25(1):152. doi: 10.1186/s12885-025-13485-6.
This study seeks to elucidate the causal relationship between major coronary heart disease events (MCHDE) and lung cancer incidence through mendelian randomization (MR), with the goal of providing evidence to inform more effective lung cancer screening and prevention strategies.
Utilizing data from the IEU OpenGWAS project and FinnGen, this study employed a two-sample MR approach, with genetic variants serving as instrumental variables. Relevant single nucleotide polymorphisms (SNPs) associated with MCHDE and lung cancer were carefully selected, with particular attention given to mitigating potential confounders, such as smoking behaviors and statin use.
The MR analysis, utilizing FinnGen's MCHDE as the exposure factor, revealed a significant reduction in the incidence of non-small cell lung cancer (NSCLC) [odds ratio (OR) 0.893, 95% confidence interval (CI) 0.800-0.998] and small cell lung cancer (SCLC) [OR 0.684, 95% CI 0.500-0.936], highlighting the protective effect of MCHDE against these cancer subtypes. However, this protective effect was not observed for other types of lung cancer. Furthermore, substituting FinnGen's MCHDE with that from IEU OpenGWAS did not yield similar protective effects across various lung cancer subtypes.
This study suggests that MCHDE reduce the risk of NSCLC in the U.K. population and SCLC in the Finnish population. However, given that the underlying mechanism through which MCHDE reduces the risk of NSCLC and SCLC remains unclear, it is premature to conclude that individuals exposed to MCHDE do not require lung cancer screening.
本研究旨在通过孟德尔随机化（MR）阐明主要冠心病事件（MCHDE）与肺癌发病率之间的因果关系，目的是提供证据以指导更有效的肺癌筛查和预防策略。
本研究利用IEU OpenGWAS项目和芬兰基因库（FinnGen）的数据，采用两样本MR方法，将基因变异用作工具变量。仔细选择了与MCHDE和肺癌相关的单核苷酸多态性（SNP），特别注意减轻潜在的混杂因素，如吸烟行为和他汀类药物的使用。
以芬兰基因库的MCHDE作为暴露因素的MR分析显示，非小细胞肺癌（NSCLC）的发病率显著降低[比值比（OR）0.893，95%置信区间（CI）0.800 - 0.998]，小细胞肺癌（SCLC）的发病率也显著降低[OR 0.684，95%CI 0.500 - 0.936]，突出了MCHDE对这些癌症亚型的保护作用。然而，对于其他类型的肺癌未观察到这种保护作用。此外，用IEU OpenGWAS的MCHDE替代芬兰基因库的MCHDE，在各种肺癌亚型中未产生类似的保护作用。
本研究表明，MCHDE可降低英国人群中NSCLC和芬兰人群中SCLC的风险。然而，鉴于MCHDE降低NSCLC和SCLC风险的潜在机制尚不清楚，如果得出暴露于MCHDE的个体不需要进行肺癌筛查的结论还为时过早。
