Causal effect of beta-blockers on the risk of lung cancer: a Mendelian randomization study

Yi Lu; Jiachun Luo; Zhenyu Huo; Fan Ge; Yang Chen; Ying Chen; Qing Zhang; Caichen Li; Jinhui Wang; Jiayu Gan; Ziqiu Cheng; Yangbin Li; Yi Feng; Qiyuan Hu; Jianxing He; Wenhua Liang

doi:10.21037/jtd-23-1098

Causal effect of beta-blockers on the risk of lung cancer: a Mendelian randomization study

J Thorac Dis. 2023 Dec 30;15(12):6651-6660. doi: 10.21037/jtd-23-1098. Epub 2023 Dec 21.

Authors

Yi Lu^#^{1

2}, Jiachun Luo^#³, Zhenyu Huo^#⁴, Fan Ge^#⁵, Yang Chen^#⁶, Ying Chen^#², Qing Zhang^#², Caichen Li², Jinhui Wang⁷, Jiayu Gan⁸, Ziqiu Cheng⁵, Yangbin Li⁵, Yi Feng², Qiyuan Hu⁹, Jianxing He^{2

10}, Wenhua Liang^{2

11}

Affiliations

¹ Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China.
³ School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
⁴ State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁵ First Clinical School, Guangzhou Medical University, Guangzhou, China.
⁶ Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.
⁷ Second Clinical School, Wenzhou Medical University, Wenzhou, China.
⁸ Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁹ First Clinical Medical School, the First Hospital, Shanxi Medical University, Taiyuan, China.
¹⁰ Department of Thoracic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, China.
¹¹ Department of Oncology, the First People's Hospital of Zhaoqing, Zhaoqing, China.

^# Contributed equally.

Abstract

Background: It remains uncertain whether there is a causal association of the use of beta-blockers (BBs) on lung cancer risk. We used a two-sample Mendelian randomization (MR) approach to identify the causal association of BBs and lung cancer risk.

Methods: Twenty-two BB-related single-nucleotide polymorphisms (SNPs) were obtained from the UK Biobank as the instrumental variables (IVs). Genetic summary data information of lung cancer was extracted from the International Lung Cancer Consortium, with a total of 11,348 cases and 15,861 controls. We adopted the inverse-variance weighted (IVW) approach to conduct the MR analyses. Egger-intercept analysis was further performed as sensitivity analysis for pleiotropy evaluation. Additionally, we investigated whether BBs could causally affect the risk of lung cancer through their pharmacological effects.

Results: The current IVW analysis suggested a decreased lung cancer risk in BB users [odds ratio (OR) =0.83; 95% confidence interval (CI): 0.73-0.95; P<0.01]. Results of Egger-intercept analysis demonstrated that no pleiotropy was found (P=0.94), which suggested the robustness of the causality. However, there was little evidence that pharmacological effects mediate the association between BBs and lung cancer.

Conclusions: The current analysis suggested that BBs could decrease the risk of lung cancer but may be not via its pharmacological effects. Further research is in need for elucidating the underlying mechanisms.

Keywords: Mendelian randomization (MR); beta-blockers (BBs); lung cancer; risk factors.