A two-sample mendelian randomization study of non-tuberculous mycobacteria infection and lung cancer.

Abstract

Background: Non-tuberculous mycobacterial lung disease may coexist or precede lung cancer, yet a causal link remains unproven. This study aimed to elucidate the causal association between non-tuberculous mycobacteria (NTM) and lung cancer.

Methods: Summary data from genome-wide association studies (GWAS) for NTM, atypical mycobacterial lung infections, and various types of lung cancer were utilized. A two-sample Mendelian randomization (MR) design was applied using the inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger regression methods. Sensitivity analysis and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to detect and correct for horizontal pleiotropy. The leave-one-out analysis was used to evaluate the robustness of the results.

Results: The IVW results showed no significant causal relationships between NTM infection and the risk of lung cancer and between atypical mycobacterial lung infection and the risk of lung cancer. The results of the weighted median, weighted mode, and MR-Egger regression methods aligned with those of the IVW method. Cochran's Q test revealed that heterogeneity significantly influenced the association between NTM pulmonary infections and lung cancer. The MR-PRESSO analysis identified two outlier instrumental variables (IVs); after excluding them, the results remained similar, without causal associations.

Conclusions: The findings of this study do not support a genetically causal relationship between NTM and atypical mycobacterial lung infections with lung cancer.