Abstract
BACKGROUND: Frailty and unfavorable lifestyle factors are associated with elevated cancer risk. However, whether adherence to a healthy lifestyle is associated with a reduction in frailty-related cancer risk remains unclear. This study aimed to examine the associations between frailty, healthy lifestyle, and overall cancer risk, and to assess the extent to which a healthy lifestyle is correlated with attenuated risks of overall and site-specific cancers associated with frailty. METHODS: This prospective cohort study utilized data from the China Kadoorie Biobank (CKB), enrolling 484,225 adults aged 30-79 years from 10 geographically diverse regions across China. The frailty index (FI) was calculated using 28 baseline variables, all of which represented health status deficits measured through questionnaires and physical examinations. Lifestyle behaviors were determined by smoking status, alcohol consumption, physical activity, diet score, and body shape. The primary outcome was incidence of all cancer types during follow-up (ICD-10: C00-C97). Multivariable-adjusted Cox proportional hazards regression models were used to evaluate associations between frailty, healthy lifestyle, and cancer risk. RESULTS: Among 484,225 participants in the China Kadoorie Biobank cohort, 288,531 (59.6%) were women. After 4,774,217 person-years of follow-up, 21,459 incident cancer cases were identified. Participants with high frailty showed significantly increased risk of overall cancer (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.23-1.38). Conversely, adherence to a favorable lifestyle was associated with reduced cancer risk (HR 0.74, 95% CI 0.71-0.78). Additive interaction analysis demonstrated a significant negative interaction between frailty and favorable lifestyle regarding overall cancer risk (RERI: - 0.50, 95% CI: - 0.75, - 0.24). Most notably, we found that adherence to a healthy lifestyle was significantly associated with a reduction in the detrimental effects of frailty on overall cancer risk. Specifically, Participants with robust status and a favorable lifestyle exhibited the lowest cancer risk (HR 0.57, 95% CI 0.51-0.63, P < 0.001). Furthermore, similar protective associations were observed for site-specific cancers, including lung, colorectal, and liver cancers. CONCLUSION: In this large-scale prospective cohort study of Chinese adults, we demonstrated that adherence to a healthy lifestyle was significantly associated with a reduced risk of frailty-related cancer. Our findings highlight the importance of integrating healthy lifestyle factors into cancer prevention strategies for frail populations.