BACKGROUND: While age is an important risk factor for both cancer and frailty, it is unclear whether cancer itself increases the risk of frailty. We aimed to assess the association between cancer and frailty in a longitudinal cohort of older Danish twins, taking familial effect into account. METHODS: Using the Danish Cancer Registry, cancer cases were identified among participants aged 70 and over in the Longitudinal Study of Aging Danish Twins (LSADT). Frailty was evaluated over 10 years of follow-up using the frailty index (FI) and defined as FI > 0.21. Stratified Cox regressions were performed on discordant twin pairs (pairs where one twin had incident cancer and the other was cancer-free), and on all LSADT individual twins (twin pairs and singletons) with no history of cancer. RESULTS: Among the 72 discordant pairs (n=144, median age at inclusion=75) included in the study, the median FI at inclusion was 0.08 for both cancer twins and cancer-free co-twins. From the stratified Cox regression, twins with cancer had an increased hazard of developing frailty (HR=3.67, 95%CI=1.02,13.14) compared to their cancer-free co-twins. The analyses on individual twins (n=4,027) provided similar results, showing an increased hazard of frailty in individuals with cancer (HR=2.57, 95%CI= 1.77,3.74) compared to those without cancer. CONCLUSIONS: We showed a higher risk of becoming frail following a cancer diagnosis in both discordant twin pairs and individual twins. These findings support the importance of monitoring of frailty in older adults with cancer through geriatric assessments and implementation of frailty interventions.< Réduire