Global mortality and disability burden of young-onset non-colorectal gastrointestinal cancers, 1990–2021.

e16476 Background: The incidence of gastrointestinal (GI) cancers among adults younger than 50 years has risen worldwide. While trends in early-onset colorectal cancer (CRC) are well documented, the burden of non-colorectal GI malignancies in younger populations remains poorly characterized across sociodemographic contexts. Methods: Using Global Burden of Disease (GBD) 2021 data, we quantified mortality and disability-adjusted life-years (DALYs) for gastric, liver, pancreatic, gallbladder/biliary, and esophageal cancers among individuals aged 15–49 years from 1990–2021. Age-standardized mortality rates (ASMRs) and DALY rates were evaluated across socio-demographic Index (SDI) quintiles. Temporal trends were assessed using linear regression to estimate average annual percent change (AAPC) with corresponding 95% confidence intervals. Results: From 1990–2021, young-onset non-colorectal GI cancers caused 7,311,542 deaths globally, led by gastric (3,203,746; 43.8%), liver (1,874,358; 25.6%), and esophageal cancers (1,223,473; 16.7%). Gastric cancer contributed 3,203,746 deaths, with the highest DALY burden (147.9; 95%CI:128.5–163.3), global ASMR 3.0 (95%CI:2.6–3.3), and peak mortality in high-middle SDI regions (ASMR 3.2; 95%CI:2.6–3.7); both mortality and DALYs declined over time. Liver cancer accounted for 1,874,358 deaths (ASMR 1.7; 95% CI:1.6–1.9; DALYs 85.6; 95% CI 77.9–94.8), with highest mortality in the high-middle (ASMR 2.2; 95% CI 1.8–2.7) and middle SDI regions (2.0; 95% CI 1.7–2.5) and increasing mortality in low-middle SDI regions (AAPC 0.3; 95% CI 0.2–0.4). Esophageal cancer caused 1,223,473 deaths (ASMR 1.1; 95% CI 1.0–1.2; DALYs 54.1; 95% CI 49.6–58.7), with highest mortality in high-middle SDI regions (ASMR 1.3 95% CI 1.0–1.6) and overall global declines. Pancreatic cancer mortality increased globally (AAPC 0.1; 95% CI 0.1–0.2), driven by sharp rises in low-middle SDI regions (AAPC 1.6; 95% CI 1.6–1.6) and middle SDI regions (1.2; 95% CI 1.1–1.3), and showed the highest mortality in high-middle (ASMR 1.4; 95% CI 1.2–1.6) and high SDI regions (1.1; 95% CI 1.0–1.2), with DALYs 32.9 (95% CI 31.2–34.7). Gallbladder and biliary cancers had the lowest burden (DALYs 11.4; 95% CI 9.0–12.8), but mortality increased in low-middle (AAPC 0.6; 95% CI 0.5–0.6) and middle SDI regions (AAPC 0.2; 95 %CI 0.1–0.2). Conclusions: Substantial increases in young-onset pancreatic and hepatobiliary cancer mortality in lower-middle SDI regions reflect shifting global epidemiology. Geographic disparities in gastric, liver, and pancreatic cancer burdens highlight the need for targeted prevention and improved early detection strategies beyond colorectal cancer. AAPC in age-standardized mortality rates by SDI region. Cancer Type High SDI High-middle SDI Middle SDI Low-middle SDI Low SDI Stomach ↓ ↓ ↓ ↓ ↓ Esophageal ↓ ↓ ↓ ↓ ↓ Liver ↓ ↓ ↓ ↑ ↓ Pancreatic ↓ ↑ ↑ ↑↑ ↑ Gallbladder/Biliary ↓ ↓ ↑ ↑ ↓