BackgroundThere is a causal relationship between many non-communicable diseases and other infectious diseases. However, the exact relationship between lung cancer and the immune response to antibodies associated with viral diseases is unclear. Compared with other traditional methods, Mendelian randomization (MR) studies reduce the influence of confounding factors, thus improving the accuracy of the results. This study used MR to investigate the relationship between lung cancer and its subtypes, and the antibody immune response.MethodsA two-sample MR method was employed to examine the association between lung cancer, its subtypes, and antibody-mediated immunity linked to 46 infectious diseases. The instrumental variables were single nucleotide polymorphisms associated with lung cancer and its subtypes. Various MR methods were used to study the causal relationship between lung cancer risk and exposure, including weighted median, MR-Egger regression, inverse variance weighting, simple model and simple median methods. In addition, immunocytological analyses were performed on lung cancer and its subtypes.ResultsThis study investigated the relationship between lung cancer and antibodies to varicella zoster glycoproteins I and E. This indicates that the level of these antibodies is a risk factor for lung cancer. The levels of antibodies to human herpes virus 7 U14, varicella zoster virus glycoproteins I and E, and anti-polyoma virus 2 were found to be related to squamous cell carcinoma, indicating a risk factor for lung cancer. Furthermore, the antibody levels of Epstein-Barr virus EBNA1 and Epstein-Barr virus VCA p18 were found to be related to lung squamous cell carcinoma and act as a protective factor. Another causal relationship was noted between small cell lung cancer and Epstein-Barr virus ZEBRA antibody levels, identifying ZEBRA as a risk factor. Leave-one-out sensitivity analysis and pleiotropy tests confirmed the stability of the results. Meanwhile, differences in the distribution of immune cells between different lung cancer subtypes provide further support for the MR results.ConclusionThis study established a causal relationship between infectious disease-related antibody immune responses and lung cancer and its subtypes via genetic methods, increasing the understanding of the role of infectious disease-related antibody immune responses in lung cancer.