The association between the number of chronic diseases and cancer: the mediating role of frailty

Chronic multimorbidity is linked to elevated cancer risk, but the underlying pathways remain unclear. This study aimed to examine the association between the number of chronic diseases and cancer and to assess the potential mediating role of frailty. Data from the 2011 to 2015 China Health and Retirement Longitudinal Study involving 16 848 participants for cross-sectional analysis and 12 702 for longitudinal follow-up were used. Frailty was assessed using a 32-item frailty index. Multivariable logistic and Cox proportional hazards regressions assessed associations between chronic disease count (0, 1, ≥2) and cancer prevalence/incidence. A mediation analysis quantified frailty's mediating effect. After full adjustment, having two or more chronic diseases was significantly associated with higher cancer prevalence [odds ratio (OR) = 1.94, 95% confidence interval (CI): 1.22-3.08, P = 0.005) and elevated risk of incident cancer (hazard ratio = 1.96, 95% CI:1.17-3.28, P = 0.010). These associations remained consistent across subgroups stratified by demographic characteristics and lifestyle factors. Frailty itself was independently associated with cancer outcomes (prevalence OR = 5.19, incidence hazard ratio = 2.04) and mediated 34.28% of the total effect (β = 0.0007, 95% CI: 0.0004-0.0012, P < 0.0001). An elevated number of chronic diseases is associated with an increased risk of cancer, and frailty itself is a strong independent risk factor for cancer. Importantly, frailty acts as a key mediator. Interventions targeting frailty may help mitigate cancer risk in individuals with chronic multimorbidity.