Huang Yiming, Lin Zhi, Huang Ting, Zhou Heran
Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou TCM Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Department of Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, China.
Front Oncol. 2024 Aug 16;14:1452559. doi: 10.3389/fonc.2024.1452559. eCollection 2024.
Previous clinical evidence has shown a correlation between pulmonary fibrosis (PF) and lung cancer (LC), but their causal relationship remains unknown.
This study utilized a bidirectional two-sample Mendelian randomization (MR) approach to explore the causal relationship between PF and LC, including its subtypes. Genetic data were obtained from the IEU and FinnGen Genome-Wide Association Studies (GWAS). SNPs with genome-wide significance were selected, and analyses were conducted using Inverse-Variance Weighted (IVW), MR Egger, and Weighted Median methods. The IVW results for various subtypes of lung cancer and PF were used in a meta-analysis to investigate the overall causal effect between PF and lung cancer. Sensitivity analysis was used for both MR and meta-analysis to investigate the robustness of the results.
The bidirectional MR analysis showed no significant causal relationship between PF and overall, LC or its subtypes, except for SCLC, which had a significant positive association (OR = 1.29, 95% CI 1.07-1.57, p = 0.009). The meta-analysis results indicated no overall causal effect (OR = 1.067, 95% CI: 0.952-1.195, P = 0.265, I² = 57.3%). In the reverse MR analysis, NSCLC and LUSC showed significant associations with PF (OR = 1.12, 95% CI 1.01-1.23, p = 0.028 and OR = 1.04, 95% CI 1.01-1.08, p = 0.012, respectively), while the meta-analysis results indicated no significant causal effect (OR = 1.006, 95% CI: 0.973-1.040, P = 0.734, I² = 55.9%). Sensitivity analyses indicated no evidence of horizontal pleiotropy or significant heterogeneity.
This study suggests a potential causal relationship between PF and SCLC, as well as between NSCLC and LUSC with PF. However, the overall causal relationship between PF and LC was not statistically significant, possibly due to individual variability and other influencing factors. Further research using data from diverse populations is needed to validate these findings.
既往临床证据显示肺纤维化（PF）与肺癌（LC）之间存在相关性，但其因果关系仍不明确。
本研究采用双向双样本孟德尔随机化（MR）方法探讨PF与LC及其亚型之间的因果关系。遗传数据来自IEU和芬兰基因组全基因组关联研究（GWAS）。选择具有全基因组显著性的单核苷酸多态性（SNP），并使用逆方差加权（IVW）、MR Egger和加权中位数方法进行分析。肺癌和PF各亚型的IVW结果用于荟萃分析，以研究PF与肺癌之间的总体因果效应。敏感性分析用于MR和荟萃分析，以研究结果的稳健性。
双向MR分析显示，除小细胞肺癌（SCLC）有显著正相关（比值比[OR]=1.29，95%置信区间[CI]1.07-1.57，P=0.009）外，PF与总体LC、其亚型之间无显著因果关系。荟萃分析结果表明无总体因果效应（OR=1.067，95%CI：0.952-1.195，P=0.265，I²=57.3%）。在反向MR分析中，非小细胞肺癌（NSCLC）和肺鳞癌（LUSC）与PF有显著关联（分别为OR=1.12，95%CI 1.01-1.23，P=
