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

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 personalized medicine in gastric cancer care, focusing on molecular targeted therapies and immunotherapy. This review also highlights the critical need for better screening methods that could facilitate early detection and treatment, potentially improving the prognosis. By integrating epidemiological insights with new therapeutic strategies, this article aims to thoroughly understand of gastric cancer's dynamics and outline a framework for future research and clinical management, advocating for a multidisciplinary approach to tackle this formidable disease.