Global Burden of Early-Onset Cancers Attributable to Metabolic Risk Factors from 1990 to 2021 and Projections to 2040

Background: Early-onset cancers (diagnosed in individuals under 50 years of age) are increasingly contributing to the global cancer burden. Among the known contributors, specific metabolic risk factors-namely high body mass index (BMI) and high fasting plasma glucose (FPG)-have emerged as significant determinants. This study assessed the global burden of early-onset cancers attributable to these two metabolic risk factors and projected their trends through 2040. Methods: Using data from the Global Burden of Disease 2021 study, we analyzed mortality, disability-adjusted life years (DALYs), and estimated annual percentage changes for early-onset cancers linked to metabolic risk factors, stratified by age, sex, and sociodemographic index (SDI). Future trends were projected based on these data. Results: In 2021, the two metabolic risk factors (high FPG and high BMI) together accounted for 34,112 (95% uncertainty interval [UI], 15,037 to 54,888) deaths and 1,691,418 (95% UI, 762,923 to 2,698,657) DALYs from early-onset cancers, corresponding to mortality and DALY rates of 0.9 (95% UI, 0.4 to 1.4) and 42.8 (95% UI, 19.3 to 68.3) per 100,000 population, respectively. Between 1990 and 2021, both mortality and DALY rates rose significantly, with the greatest increases observed in individuals aged 30-34 years and in low-middle SDI regions. High FPG and high BMI were the leading contributors, with colorectal cancer showing the highest burden and liver cancer the most rapid growth. While high BMI predominated in most SDI regions, high FPG was more prominent in low-SDI countries, particularly among females. Projections indicate a continued rise in mortality and DALY rates through 2040. Conclusion: High BMI and high FPG are major contributors to the global burden of early-onset cancers, with marked sex and socioeconomic disparities necessitating targeted interventions. Urgent strategies are required to mitigate metabolic risks and enhance early cancer detection, especially among vulnerable populations.