Causal association of antibody-mediated immune responses to infectious disease agents with lung cancer: a Mendelian randomization study

Abstract Background There 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, Mende...

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Main Authors: Guicai Liang, Lyubo Wang, Zhiqiang Wang, Tao Li, Lei Jiang, Yuncheng Bai, Lei Yang, Yi Feng, Yan Li, Meng Yang, Jiling Chang, Haiyue Yang, Xilong Zhou, Lincan Duan, Chunlei Ge
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Language:English
Published: Springer 2025-07-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02997-z
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author Guicai Liang
Lyubo Wang
Zhiqiang Wang
Tao Li
Lei Jiang
Yuncheng Bai
Lei Yang
Yi Feng
Yan Li
Meng Yang
Jiling Chang
Haiyue Yang
Xilong Zhou
Lincan Duan
Chunlei Ge
author_facet Guicai Liang
Lyubo Wang
Zhiqiang Wang
Tao Li
Lei Jiang
Yuncheng Bai
Lei Yang
Yi Feng
Yan Li
Meng Yang
Jiling Chang
Haiyue Yang
Xilong Zhou
Lincan Duan
Chunlei Ge
author_sort Guicai Liang
collection DOAJ
description Abstract Background There 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. Methods A 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. Results This 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. Conclusion This 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.
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spelling doaj-art-5b7278439ab34d56ac20afd1bb6400492025-08-20T03:38:15ZengSpringerDiscover Oncology2730-60112025-07-0116111910.1007/s12672-025-02997-zCausal association of antibody-mediated immune responses to infectious disease agents with lung cancer: a Mendelian randomization studyGuicai Liang0Lyubo Wang1Zhiqiang Wang2Tao Li3Lei Jiang4Yuncheng Bai5Lei Yang6Yi Feng7Yan Li8Meng Yang9Jiling Chang10Haiyue Yang11Xilong Zhou12Lincan Duan13Chunlei Ge14Cancer Biotherapy Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital YunnanCardiothoracic Surgery Department, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital YunnanDepartment of Radiation Oncology, The First Affiliated Hospital of Kunming Medical UniversityCancer Biotherapy Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital YunnanCancer Biotherapy Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital YunnanDepartment of Orthopedic Surgery, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and TechnologyDepartment of Oncology, The People′s Hospital of Dehong Prefecture, Dehong Hospital Affiliated to Kunming Medical UniversityCancer Biotherapy Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital YunnanDepartment of Radiation Oncology, The First Affiliated Hospital of Kunming Medical UniversityCancer Biotherapy Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital YunnanCancer Biotherapy Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital YunnanCancer Biotherapy Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital YunnanCancer Biotherapy Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital YunnanPuer City People’s HospitalCancer Biotherapy Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital YunnanAbstract Background There 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. Methods A 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. Results This 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. Conclusion This 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.https://doi.org/10.1007/s12672-025-02997-zAntibody-mediated immune responses to infectious disease agentsLung cancerMendelian randomizationGenome-wide association studies
spellingShingle Guicai Liang
Lyubo Wang
Zhiqiang Wang
Tao Li
Lei Jiang
Yuncheng Bai
Lei Yang
Yi Feng
Yan Li
Meng Yang
Jiling Chang
Haiyue Yang
Xilong Zhou
Lincan Duan
Chunlei Ge
Causal association of antibody-mediated immune responses to infectious disease agents with lung cancer: a Mendelian randomization study
Discover Oncology
Antibody-mediated immune responses to infectious disease agents
Lung cancer
Mendelian randomization
Genome-wide association studies
title Causal association of antibody-mediated immune responses to infectious disease agents with lung cancer: a Mendelian randomization study
title_full Causal association of antibody-mediated immune responses to infectious disease agents with lung cancer: a Mendelian randomization study
title_fullStr Causal association of antibody-mediated immune responses to infectious disease agents with lung cancer: a Mendelian randomization study
title_full_unstemmed Causal association of antibody-mediated immune responses to infectious disease agents with lung cancer: a Mendelian randomization study
title_short Causal association of antibody-mediated immune responses to infectious disease agents with lung cancer: a Mendelian randomization study
title_sort causal association of antibody mediated immune responses to infectious disease agents with lung cancer a mendelian randomization study
topic Antibody-mediated immune responses to infectious disease agents
Lung cancer
Mendelian randomization
Genome-wide association studies
url https://doi.org/10.1007/s12672-025-02997-z
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