Gastric Cancer: Epidemiology, Risk Factors, Pathogenesis, Clinical Features, Diagnosis, and Management

Gastric cancer is a multifactorial disease shaped by diverse risk factors and a complex pathogenesis spanning from chronic atrophic gastritis to invasive malignancy. Its global incidence shows marked geographic disparities, and advances in understanding its pathogenic mechanisms have improved diagnosis and treatment. Although the relationship between gastric cancer and macrophages has been extensively investigated, a systematic review integrating the entire clinical and biological continuum of gastric cancer, from epidemiology to management, with a focus on macrophages remains lacking. This review summarizes the epidemiology and multidimensional risk factors for gastric cancer, including infectious, dietary, genetic, microbiome, and metabolite-related factors. We describe the evolution of precancerous conditions, molecular alterations such as miRNA expression, and the bidirectional interactions between gastric cancer cells and macrophages that drive tumor progression within the tumor microenvironment. We also review clinical features, diagnostic approaches based on screening and endoscopy, and current management strategies, including surgery, systemic therapies, targeted therapies, immunotherapy, macrophage-targeted therapies, macrophage metabolic reprogramming, and recent preclinical and clinical advances. Overall, this review integrates evidence from epidemiology, molecular biology, immunology, and pathology to provide a comprehensive framework for understanding gastric cancer pathogenesis and current as well as emerging therapeutic strategies.