Endurance and power genes modify the protective effect of fast walking pace on lung cancer risk: a UK Biobank prospective cohort study

BackgroundTo investigate the association between walking pace and lung cancer risk, and explore whether any association is modified by endurance and power-related genes. MethodsWe followed up 449,890 UK Biobank participants free of cancer at baseline. Data on self-reported walking pace were collected by touchscreen questionnaire at baseline. Blood samples were obtained for genotyping. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for lung cancer incidence and mortality, with slow walking pace as the reference. Findings4,087 lung cancer incident cases and 2,245 lung cancer deaths were identified during a median follow-up period of 12.1 and 12.7 years, respectively. For incident lung cancer, HR (95% CI) were 0.71 (0.65- 0.78) and 0.55 (0.49-0.61) among participants with steady and brisk walking pace, respectively. For lung cancer mortality, steady and brisk walking paces were associated with 32% and 48% lower risks, respectively. Associations of walking pace with risks of lung cancer occurrence and mortality were modified by rs1815739 in ACTN3 and rs7191721 in RBFOX1. The protective effect of faster walking pace was more evident among participants carrying a higher number of T allele for rs1815739 in ACTN3 (Pinteraction=0.04 for both lung cancer incidence and mortality) and A allele for rs7191721 in RBFOX1 (Pinteraction=0.01 for lung cancer incidence, Pinteraction=0.004 for lung cancer mortality). InterpretationFaster walking pace is associated with lower risks of both lung cancer occurrence and mortality, and this protective effect is modulated by polymorphisms in endurance gene RBFOX1 and in power gene (ACTN3). FundingThis work was supported by grants from the China Postdoctoral Science Foundation (Grant No. BX2021021, 2022M710249), Fujian Provincial Health Technology Project (Grant No. 2020CXB009), and the Natural Science Foundation of Fujian Province, China (Grant No. 2021J01352).