ABSTRUCT Background Understanding the intercontinental and regional cancer burden attributable to modifiable risk factors is crucial for developing effective prevention strategies. Using GBD 2021 data, this study aims to identify disparities in cancer burden, predict future trends across different continents, and inform targeted interventions. Methods This study utilized the GBD 2021 framework to comprehensively assess the cancer burden across four world regions, with a focus on age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and disability-adjusted life years (DALYs). We systematically analyzed cancer-related risk factors using associations extracted from the GBD database. Through the application of average annual percent change (AAPC) and the Bayesian age-period-cohort (BAPC) model, we evaluated the cancer burden in each region from 2022 to 2035. Findings In 2021, cancer incidence and mortality rates varied widely across continents. The Americas led with an incidence of 1,633.49 per 100,000 and a mortality rate of 116.097, while Europe showed 950.248 and 132.578, respectively. Asia reported 636.893 incidence and 112.329 mortality, and Africa recorded the lowest rates at 332.175 and 98.594. High mortality is associated with elevated DALYs, notably in Europe with 3,284.53 DALYs per 100,000, reflecting the highest cancer burden. In high-income regions, lifestyle-related cancers-linked to smoking, colorectal, and breast cancers-prevail, while low-income areas, particularly sub-Saharan Africa, experience infection-driven cancers like cervical cancer . Younger females under 35 bear a higher cancer burden than males, but after 70, the trend reverses significantly, with men having higher mortality across all ages. Smoking is the leading mortality risk in the Americas, Europe, and Asia, while unsafe sex dominates in Africa, correlating with high cervical cancer incidence. From 1990 to 2021, high BMI and blood glucose have surged as cancer risk factors, driven by obesity and metabolic diseases. By 2035, projections indicate incidence will increase to 1,779.6 per 100,000 in the Americas, with stable mortality at 98.97, while Asia, Africa, and Europe are expected to see moderate incidence and mortality shifts, reflecting regional disparities in cancer prevention and management strategies. Interpretation This study reveals pronounced global disparities in cancer burden, shaped by economic development, healthcare access, and lifestyle factors. High-income regions, like North America and Europe, show high incidence but lower mortality rates due to robust screening and preventive measures. Conversely, low-income regions, especially sub-Saharan Africa, experience high mortality from preventable cancers, highlighting critical healthcare gaps. Gender analysis shows women have higher incidence due to screening, while men face higher mortality risks. Projected increases in incidence globally underscore the urgency for tailored cancer control strategies, focusing on prevention and healthcare access improvements across diverse socio-economic contexts.
