Trends in early-onset gastrointestinal cancers: A comprehensive analysis of US cancer statistics (2001–2021).

11182 Background: Early-onset colorectal cancer (eoCRC) has become a well-recognized phenomenon in recent years. This study aims to explore trends in other early-onset gastrointestinal cancers (eoGIC) and provide more details on sub-sites of eoCRC. Methods: The NPCR-SEER database, which covers the entire U.S. population from 2001 to 2021, was utilized to analyze GI cancer cases among individuals aged 20–49 years. Trends were assessed using Joinpoint regression, and polynomial regression was applied to forecast incidence rates from 2021 to 2031. Results: A total of 528,310 cases were analyzed. In 2021, eoCRC had the highest incidence (n=17,567), followed by stomach cancer (n=2,783) and pancreatic cancer (n=2,634). EoCRC has been significantly increasing with (Average Annual Percent Change (AAPC) 1.30%, p<0.01). Stomach and pancreatic cancers showed steady rise with (AAPC 0.73%, p<0.01) and (AAPC 1.14%, p<0.01). Among eoCRC subsites, rectal cancer showed the most substantial increase (AAPC 1.86%, p<0.01), followed by sigmoid colon (AAPC 1.17%, p<0.01) and descending colon (AAPC 0.85%, p<0.01). Although the appendiceal, small intestine and intrahepatic bile duct represent a smaller portion of the eoGICs, these sites demonstrated the most dramatic rises in incidence compared to their previous crude rates. Appendiceal cancer showed the highest increase (AAPC 7.23%, p<0.01), followed by intrahepatic bile duct cancer (AAPC 5.81%, 95% CI, p<0.01) and small intestine cancer (AAPC 2.90%, p<0.01). Declining trends were observed in esophageal (AAPC -1.50%, <0.01), liver (AAPC -2.89%, <0.01), and anal cancers (AAPC -0.98%, <0.01). By 2027, females are projected to cross males (R 2 = 0.91) in the incidence of eoGICs. Conclusions: Several eoGICs are exhibiting increasing trends, potentially indicating a shared or disease-agnostic underlying etiology. The rising prevalence and shifting demographics underscore the critical need for tailored prevention measures and early detection strategies focused on high-risk populations. Future research should focus on identifying underlying factors driving these trends. Average annual percent change of subsites of colorectal cancers 2001–2021. Primary Site AAPC p-value Cecum 0.92% <0.01 Ascending Colon 0.43% 0.10 Hepatic Flexure -1.27% <0.01 Transverse Colon 0.51% <0.01 Splenic Flexure -0.51% 0.09 Descending Colon 0.85% <0.01 Sigmoid Colon 1.17% <0.01 Rectosigmoid Junction 0.39% 0.13 Rectum 1.86% <0.01