Abstract 1155P
Background
Leisure Sedentary behaviors (LSB) are widespread and observational studies have provided emerging evidence that LSB plays 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 4 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 genetically predisposed 1.5 h increase in LSB spent on watching TV increased 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). Causal effects remained to be 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.
Conclusions
Robust evidence was demonstrated for an independent, causal effect of LSB spent on watching TV in increasing risk of LC. Further work is necessary to investigate the potential mechanisms.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
China National Science Foundation (Grant number 81871893); Key Project of Guangzhou Scientific Research Project (Grant number 201804020030). Cultivation of Guangdong College Students' Scientific and Technological Innovation (“Climbing Program” Special Funds) (Grant number pdjh2020a0480, pdjh2021a0407).
Disclosure
All authors have declared no conflicts of interest.