Univariable and Multivariable Two-Sample Mendelian Randomization Investigating the Effects of Leisure Sedentary Behaviors on the Risk of Lung Cancer

Haoxin Peng; Xiangrong Wu; Yaokai Wen; Yiyuan Ao; Yutian Li; Wenhui Guan; Jinsheng Lin; Caichen Li; Hengrui Liang; Jianxing He; Wenhua Liang

doi:10.3389/fgene.2021.742718

Univariable and Multivariable Two-Sample Mendelian Randomization Investigating the Effects of Leisure Sedentary Behaviors on the Risk of Lung Cancer

Front Genet. 2021 Nov 24:12:742718. doi: 10.3389/fgene.2021.742718. eCollection 2021.

Authors

Haoxin Peng^{1

2}, Xiangrong Wu^{1

2}, Yaokai Wen^{3

4}, Yiyuan Ao^{1

2}, Yutian Li¹, Wenhui Guan¹, Jinsheng Lin¹, Caichen Li¹, Hengrui Liang¹, Jianxing He¹, Wenhua Liang^{1

5}

Affiliations

¹ Department of Thoracic Oncology and Surgery, China State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
² Nanshan School, Guangzhou Medical University, Guangzhou, China.
³ School of Medicine, Tongji University, Shanghai, China.
⁴ Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.
⁵ Medical Oncology, the First People's Hospital of Zhaoqing, Zhaoqing, China.

Abstract

Leisure sedentary behaviors (LSB) are widespread, and observational studies have provided emerging evidence that LSB play a role in the development of lung cancer (LC). However, the causal inference between LSB and LC remains unknown. Methods: We utilized univariable (UVMR) and multivariable two-sample Mendelian randomization (MVMR) analysis to disentangle the effects of LSB on the risk of LC. MR analysis was conducted with genetic variants from genome-wide association studies of LSB (408,815 persons from UK Biobank), containing 152 single-nucleotide polymorphisms (SNPs) for television (TV) watching, 37 SNPs for computer use, and four SNPs for driving, and LC from the International Lung Cancer Consortium (11,348 cases and 15,861 controls). Multiple sensitivity analyses were further performed to verify the causality. Results: UVMR demonstrated that genetically predisposed 1.5-h increase in LSB spent on watching TV increased the odds of LC by 90% [odds ratio (OR), 1.90; 95% confidence interval (CI), 1.44-2.50; p < 0.001]. Similar trends were observed for squamous cell lung cancer (OR, 1.97; 95%CI, 1.31-2.94; p = 0.0010) and lung adenocarcinoma (OR, 1.64; 95%CI 1.12-2.39; p = 0.0110). The causal effects remained significant after adjusting for education (OR, 1.97; 95%CI, 1.44-2.68; p < 0.001) and body mass index (OR, 1.86; 95%CI, 1.36-2.54; p < 0.001) through MVMR approach. No association was found between prolonged LSB spent on computer use and driving and LC risk. Genetically predisposed prolonged LSB was additionally correlated with smoking (OR, 1.557; 95%CI, 1.287-1.884; p < 0.001) and alcohol consumption (OR, 1.010; 95%CI, 1.004-1.016; p = 0.0016). Consistency of results across complementary sensitivity MR methods further strengthened the causality. Conclusion: Robust evidence was demonstrated for an independent, causal effect of LSB spent on watching TV in increasing the risk of LC. Further work is necessary to investigate the potential mechanisms.

Keywords: Mendelian randomization; cancer prevention; leisure sedentary behaviors; lung cancer; single-neucleotide polymorphism.