Global, regional and national cancer burden and trends of middle-aged and older populations: a GBD 2021-based analysis, prediction and prevention

Background Middle-aged and older adults (MAOs; defined as individuals aged ≥40 years) account for the global cancer burden, contributing to 70–80% of cases. Characterizing cancer profiles in this demographic is essential for developing targeted prevention and treatment strategies to mitigate global impacts. Methods Using Global Burden of Diseases (GBD) 2021 data, we analyzed incidence, prevalence, mortality and Disability-Adjusted Life Years (DALYs) for 31 cancers among MAOs (aged≥40) across 204 countries/21 regions(1990-2021). Trends were quantified via Joinpoint regression, and autoregressive integrated moving-average (ARIMA) models projected the burden through 2035. Risk attribution utilized population attributable fractions across Socio-demographic Index (SDI) quintiles. An order-independent Shapley decomposition attributed projected cancer incidence changes during 2021–2035 to population growth, aging, and age-specific incidence rate shifts. Results In 2021, MAOs accounted for 48,804,114 incident cases and 9,434,210 deaths. Females exhibited a 1.14-fold higher age-standardized incidence rate (ASIR) than males, yet males had a higher age-standardized mortality rate (ASMR). Projections suggested a continued rise in cancer burden through 2035. Peak incidence occurred in ages 60–69 and the highest mortality in ages 70–79. Breast cancer was the main cancer in females; tracheal/bronchus/lung cancer in males. Tracheal/bronchus/lung cancer dominated mortality across all groups except middle-aged women (breast cancer). High-SDI regions bore the greatest burden, characterized by tracheal/bronchus/lung and colorectal cancers, while low-SDI regions shifted toward breast, cervical and stomach cancer. Risk factor analysis from 2010–2021 revealed rising metabolic risks, with high body mass index (BMI) and fasting plasma glucose-attributable DALYs increasing by 12.39% and 11.36% respectively, especially in high-SDI regions. Conversely, while most behavioral risks declined, smoking remained the leading risk factor, contributing over 60% to lung cancer DALYs. In low-SDI regions, behavioral drivers such as unsafe sex (accounting for >90% of cervical cancer risk) and air pollution remained the dominant persistent risks. Discussion This study, the first focusing on MAOs’ global cancer burden, reveals heterogeneous patterns by age, gender, and SDI. Lung cancer was the leading cause of death (smoking as main risk). Metabolic risks rose in high-SDI regions, behavioral risks in low-SDI regions. In conclusion, MAOs’ cancer burden will rise through 2035; region-specific precision strategies are essential.