Early-Onset Digestive System Cancers: Risk Factors and Clinicopathological and Molecular Features Across Organ Sites

The incidence of early-onset cancers, commonly defined as cancers diagnosed before age 50 years, has been increasing globally over recent decades. In particular, the incidence of several early-onset digestive system cancers, including cancers of the esophagus, stomach, colorectum, liver, extrahepatic bile duct, gallbladder, and pancreas, has been reported to be increasing in multiple regions. In this review, we summarize the current evidence on these characteristics, highlight shared and distinct features across organ sites, and discuss research opportunities to address the rising burden of early-onset digestive system cancers. Several early-onset cancer types appear to share risk factors, including obesity (for esophageal adenocarcinoma, gastric cancer, colorectal cancer, liver cancer, gallbladder cancer, and pancreatic cancer), alcohol (for esophageal squamous cell carcinoma, gastric cancer, colorectal cancer, and pancreatic cancer), smoking (for esophageal squamous cell carcinoma, gastric cancer, colorectal cancer, liver cancer, and pancreatic cancer), and family history of cancer (for gastric cancer, colorectal cancer, liver cancer, and pancreatic cancer). Other shared characteristics across digestive system cancer types may include infection-related cancers (e.g., EBV for gastric cancer and HBV for liver and bile duct cancers). These risk factors are shared across multiple early-onset cancer types, suggesting that exposure to these risk factors contributes to tumor development at a younger age across organ systems.