Bu Zhaoting, Chen Xinying, Liu Xiaoyue, Yin Bing, Ge Sanyu, Zheng Xin, Xu Changhong, Zhao Hong, Li Yi, Li Xiangrui, Shi Hanping
Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Center for Clinical Nutrition and Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
J Cachexia Sarcopenia Muscle. 2025 Dec;16(6):e70164. doi: 10.1002/jcsm.70164.
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.
尽管衰弱已被确定为癌症的一个潜在风险因素，但大多数先前的研究仅在单一时间点考虑衰弱状态。衰弱的动态变化与癌症发病之间的关系尚不太清楚。本研究旨在评估基线衰弱状态和衰弱状态变化与后续癌症风险的关联。
数据来源于美国一项具有全国代表性的前瞻性队列研究——健康与退休研究（HRS）。使用包含29个项目的Rockwood衰弱指数评估衰弱情况，并将其分为健康、衰弱前期或衰弱。在两年时间内确定衰弱状态的变化。通过自我报告的医生诊断确定新发癌症。使用Cox比例风险模型估计风险比（HR）和95%置信区间（CI），并对人口统计学、生活方式和健康相关协变量进行调整。
共有11661名参与者（63.1%为女性；平均年龄：67.1岁）纳入基线衰弱分析，10178名参与者（63.8%为女性；平均年龄：66.3岁）纳入衰弱变化分析。在中位随访7.2年期间，基线衰弱与新发癌症风险显著增加相关（衰弱组与健康组：HR 1.61，95%CI 1.27 - 2.02；衰弱前期组与健康组：HR 1.46，95%CI 1.17 - 1.83）。在两年的过渡期内，从健康进展为衰弱前期/衰弱状态的参与者比那些保持健康的参与者患癌风险更高（HR 2.50，95%CI 1.74 - 3.61）。相反，改善为衰弱前期或健康状态的衰弱个体相对于那些仍处于衰弱状态的个体患癌风险降低（HR 0.66，95%CI 0.48 - 0.90）。在恢复到健康状态的衰弱前期个体中也观察到类似的风险降低（HR 0.51，95%CI 0.34 - 0.76）。此外，多变量调整后，衰弱指数随时间的更大增加仍与癌症风险升高相关（ΔFI最高四分位数与最低四分位数：HR 1.35，95%CI 1.13 - 1.63；趋势p < 0.001）。
基线衰弱和衰弱状态变化均独立与癌症风险相关。衰弱进展显著增加新发癌症风险，而从衰弱中恢复与风险降低相关。这些发现强调了动态衰弱监测的重要性，并表明针对衰弱的干预措施值得研究以降低潜在的癌症风险。
