Thejus Jayakrishnan, Kimmie Ng. JAMA. 2025 Oct 21;334(15):1373-1385
Early-onset gastrointestinal (GI) cancer is typically defined as GI cancer diagnosed in individuals younger than 50 years. The incidence of early-onset GI cancer is rising globally, and early-onset GI cancers represent the most rapidly increasing early-onset cancer in the US. Worldwide, among early-onset GI cancers reported in 2022, colorectal cancer (CRC) was the most common (54.3%; 184 709 cases), followed by gastric cancer (23.8%; 80 885 cases), esophageal cancer (13.2%; 45 056 cases), and pancreatic cancer (8.6%; 29 402 cases). In the US, among early-onset GI cancers reported in 2022, 20 805 individuals were diagnosed with early-onset CRC, 2689 with early-onset gastric, 2657 with early-onset pancreatic, and 875 with early-onset esophageal cancer. Most early-onset GI cancers are associated with modifiable risk factors including obesity, poor-quality diet (eg, sugar-sweetened beverages, ultraprocessed foods), sedentary lifestyle, cigarette smoking, and alcohol consumption. Nonmodifiable risk factors include family history, hereditary syndromes (eg, Lynch syndrome), and inflammatory bowel disease for patients with early-onset CRC. Approximately 15% to 30% of early-onset GI cancers have pathogenic germline variants in genes such as DNA mismatch repair genes and BRCA1/2. All patients with early-onset GI cancers should undergo germline and somatic genetic testing to guide treatment, screen for other cancers (eg, endometrial cancer in Lynch syndrome), and assess familial risk. High-risk individuals (eg, those with Lynch syndrome, a first-degree relative with CRC, or advanced colorectal adenoma) should begin CRC screening earlier, at an age determined by the specific risk factor. The prognosis for patients with early-onset GI cancers is similar to or worse than that for patients with later-onset GI cancers, highlighting the need for improved methods of prevention and early detection.
24 Mar, 2026