Advancements in Mendelian randomization analysis of lung cancer　_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

CHEN Qingyun , FAN Qinglu , NIE Zhihao , LUO Renwei , WEI Shujian ,  XIE Songping

Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, P. R. China;

Corresponding author：

XIE Songping, Email: songping0428@126.com

Keywords：

Lung cancer; small cell lung cancer; non-small cell lung cancer; Mendelian randomization; genetic variation; review

DOI：

10.7507/1007-4848.202501073

Video：

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Abstract Full text Figures/Tables Video References Cited by

Lung cancer is a major cause of cancer mortality worldwide, but the risk factors contributing to its development are not yet fully elucidated. Deepening the understanding of the risk factors and potential complications associated with lung cancer is of significant importance for the prevention and treatment of this disease. Traditional observational clinical studies and randomized controlled trials, due to the influence of various factors, render the process of causal inference more complex and may introduce biases into the results. Compared to the traditional methods, Mendelian randomization (MR) has attracted an increasing amount of attention in lung cancer research, due to its simplicity of operation and effective control of confounding factors and reverse causality biases. This paper employs bibliometric methods to analyze the published MR studies related to lung cancer, and further summarizes and discusses the content of these studies. The findings indicate that traditional risk factors, such as lifestyle habits, nutrition, obesity, socioeconomic factors, environmental pollution, and inflammatory biomarkers, have been substantiated within the context of MR studies. Additionally, MR studies support the existence of causal relationships between lung cancer and certain gut microbiota, medications, and other systemic diseases. Despite the inherent limitations of MR studies, they nonetheless hold significant value in enhancing our comprehension of the etiology of lung cancer and in identifying potential therapeutic interventions.

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9. Carreras-Torres R, Johansson M, Haycock P C, et al. Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study. PLoS One, 2017, 12(6): e0177875.
10. Zhou W, Liu G, Hung RJ, et al. Causal relationships between body mass index, smoking and lung cancer: Univariable and multivariable Mendelian randomization. Int J Cancer, 2021, 148(5): 1077-1086.
11. Jiang L, Sun Y Q, Brumpton B M, et al. Body mass index and incidence of lung cancer in the HUNT study: Using observational and Mendelian randomization approaches. BMC Cancer, 2022, 22(1): 1152.
12. You D, Wang D, Wu Y, et al. Associations of genetic risk, BMI trajectories, and the risk of non-small cell lung cancer: A population-based cohort study. BMC Med, 2022, 20(1): 203.
13. Wu D, Zhou J, Huang Y, et al. Genetically predicted childhood body mass index and lung cancer susceptibility: A two-sample Mendelian randomization study. Cancer Med, 2023, 12(17): 18418-18424.
14. Richardson TG, Urquijo H, Holmes M, et al. Leveraging family history data to disentangle time-varying effects on disease risk using lifecourse Mendelian randomization. Eur J Epidemiol, 2023, 38(7): 765-769.
15. Yang W, Yang Y, Guo Y, et al. Obesity and risk for respiratory diseases: A Mendelian randomization study. Front Endocrinol, 2023, 14: 1197730.
16. Ding J, Tu Z, Chen H, et al. Identifying modifiable risk factors of lung cancer: Indications from Mendelian randomization. PLoS One, 2021, 16(10): e0258498.
17. Shao F, Chen Y, Xu H, et al. Metabolic obesity phenotypes and risk of lung cancer: A prospective cohort study of 450, 482 UK biobank participants. Nutrients, 2022, 14(16): 3370.
18. Yu H, Zhang X, Wen B, et al. Lipid-lowering drug targets and lung related diseases: A Mendelian randomization study. ALL LIFE, 2024, 17(1): 2329440.
19. Szlasa W, Zendran I, Zalesińska A, et al. Lipid composition of the cancer cell membrane. J Bioenerg Biomembr, 2020, 52(5): 321-342.
20. Liu K, Wang S, Zhou Y, et al. Genetic associations between circulating metabolic biomarkers and lung cancer in East Asians and Europeans. Eur J Med Res, 2023, 28(1): 158.
21. Pei Y, Xu Y, Niu W. Causal relevance of circulating adiponectin with cancer: A meta-analysis implementing Mendelian randomization. Tumour Biol, 2015, 36(2): 585-594.
22. He B, Zhao J, Zhang M, et al. Causal roles of circulating adiponectin in osteoporosis and cancers. Bone, 2022, 155: 116266.
23. Wu D, Wang Z, Wang K, et al. The association between adipokines and pulmonary diseases: A Mendelian randomization study. BMC Pulm Med, 2024, 24(1): 50.
24. Wu XR, Peng HX, Xiong S, et al. A multiethnic bidirectional Mendelian randomization study negates causal effects of C-reactive protein concentrations on lung cancer. Transl Lung Cancer Res, 2021, 10(12): 4380.
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