Changes in Frailty and Incident Cancer: Evidence From the Health and Retirement Study

Although frailty has been identified as a potential risk factor for cancer, most previous studies have only considered frailty status at a single time point. The relationship between dynamic changes in frailty and incident cancer is less well understood. This study aimed to evaluate the associations of both baseline frailty status and changes in frailty status with subsequent cancer risk.

Data were derived from the Health and Retirement Study (HRS), a nationally representative prospective cohort in the United States. Frailty was assessed using a 29-item Rockwood frailty index and categorized as robust, pre-frail or frail. Changes in frailty status were determined over a 2-year period. Incident cancer was identified through self-reported physician diagnoses. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographic, lifestyle and health-related covariates.

A total of 11 661 participants (63.1% female; mean age: 67.1 years) were included in the baseline frailty analysis, and 10 178 participants (63.8% female; mean age: 66.3 years) were included in the frailty change analysis. During a median follow-up of 7.2 years, baseline frailty was associated with a significantly increased risk of incident cancer (frail vs. robust: HR 1.61, 95% CI 1.27-2.02; pre-frail vs. robust: HR 1.46, 95% CI 1.17-1.83). Over the 2-year transition period, participants who progressed from robust to pre-frail/frail status had a higher cancer risk compared to those who remained robust (HR 2.50, 95% CI 1.74-3.61). Conversely, frail individuals who improved to pre-frail or robust status had a reduced cancer risk relative to those who remained frail (HR 0.66, 95% CI 0.48-0.90). Similar risk reduction was observed among pre-frail individuals who recovered to robust status (HR 0.51, 95% CI 0.34-0.76). Additionally, greater increases in frailty index over timeremained associated with elevated cancer risk after multivariable adjustment (highest vs. lowest quartile of ΔFI: HR 1.35, 95% CI 1.13-1.63; p for trend < 0.001).

Both baseline frailty and changes in frailty status are independently associated with cancer risk. Frailty progression significantly increases the risk of incident cancer, whereas recovery from frailty is associated with reduced risk. These findings underscore the importance of dynamic frailty monitoring and suggest that interventions targeting frailty warrant investigation for potential cancer risk reduction.