Gastric cancer—Epidemiology, modifiable and non-modifiable risk factors, challenges and opportunities: An updated review

•Gastric cancer has high mortality and incidence rates, particularly in Eastern Asia, Eastern Europe, and South America.•The disease is influenced by modifiable factors (e.g., H. pylori infection, obesity, dietary habits) and nonmodifiable factors (e.g., genetics, age, male gender).•Effective treatment is complicated by late-stage diagnosis and disease heterogeneity, with current strategies including surgery, chemotherapy, radiotherapy, and targeted therapies.•The FLOT regimen is now standard for resectable cases, and treatments like trastuzumab and immune checkpoint inhibitors offer promising results.•Emphasis on personalized medicine and better screening methods is crucial for improving early detection, treatment outcomes, and overall survival rates in gastric cancer care. Gastric cancer represents a significant global health challenge due to its high mortality and incidence rates, particularly in Eastern Asia, Eastern Europe, and South America. This comprehensive review synthesizes the latest epidemiological data and explores both modifiable and non-modifiable risk factors associated with gastric cancer, aiming to delineate the multifactorial etiology of this disease. Modifiable risk factors include Helicobacter pylori infection, obesity, dietary habits, smoking and alcohol consumption, whereas nonmodifiable factors comprise genetic predispositions, age, family history and male gender. The interplay of these factors significantly impacts the risk and progression of gastric cancer, suggesting potential preventive strategies. The challenges in treating gastric cancer are considerable, largely because of the late-stage diagnosis and the heterogeneity of the disease, which complicate effective treatment regimens. Current treatment strategies involve a combination of surgery, chemotherapy, radiotherapy, and targeted therapies. The FLOT regimen (5-FU, Leucovorin, Oxaliplatin and Docetaxel) is now a standard for resectable cases in Europe and the US, showing superior survival and response rates over ECF and ECX regimens. For HER2-positive gastric cancer, trastuzumab combined with chemotherapy improves overall survival, as demonstrated by the ToGA trial. Additionally, immune checkpoint inhibitors like pembrolizumab and nivolumab offer promising results. However, the five-year survival rate remains low, underscoring the urgency for improved therapeutic approaches. Recent advancements in molecular biology and cancer genomics have begun to pave the way for persona