Early-Onset Gastrointestinal Cancers: A Review.

Importance: 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. Observations: 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. Treatment for early-onset GI cancers is similar to later-onset GI cancers and may include chemotherapy, surgery, radiation, and therapies such as poly-adenosine diphosphate ribose polymerase inhibitors for BRCA-associated pancreatic cancer. Compared with GI cancers diagnosed after age 50 years, patients with early-onset GI cancers typically receive more treatments but often have similar or shorter survival. Specialized centers and multidisciplinary teams can support patients with challenges around fertility preservation, parenting with cancer, financial difficulty, and psychosocial distress. Currently, screening is not recommended for most early-onset GI cancers, although in the US, screening for CRC is recommended for average-risk individuals starting at age 45 years. 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. Conclusions and Relevance: Early-onset GI cancers, typically defined as cancer diagnosed in individuals younger than 50 years, are among the largest subset of early-onset cancers globally. Treatment is similar to later-onset GI cancers and typically involves a combination of chemotherapy, surgery, and radiation, depending on the cancer type and stage. 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.