Gastric cancer remains a significant global health issue, being the fourth most common cancer and the second leading cause of cancer death worldwide. Despite a decline in incidence in the US and elsewhere over the past several decades, gastric cancer incidence and mortality have varied by tumor location and histology. Distal, intestinal-type gastric cancers have declined, while proximal, diffuse-type adenocarcinomas of the gastric cardia have increased, particularly in Western countries. Incidence varies by geographic location, race, and socioeconomic status, with distal gastric cancer more common in developing countries, among blacks, and in lower socioeconomic groups, while proximal tumors are more common in developed countries, among whites, and in higher socioeconomic classes. These differing trends suggest that the two types of gastric cancer may have distinct etiologies. The main risk factors for distal gastric cancer include Helicobacter pylori (H. pylori) infection and dietary factors, while gastroesophageal reflux disease (GERD) and obesity are significant in the development of proximal stomach cancer. H. pylori infection is a major contributor to gastric cancer, with a strong association between chronic H. pylori infection and the development of gastric cancer. The prevalence of H. pylori infection is linked to socioeconomic factors, and its decline in developed countries has paralleled the decrease in gastric cancer incidence. Dietary factors such as high salt intake and low consumption of fresh fruits and vegetables are also associated with increased gastric cancer risk. H. pylori infection can facilitate the growth of nitrosating bacteria, which produce carcinogenic N-nitroso compounds. Salt-preserved foods and dietary nitrite are potentially carcinogenic and may act synergistically with H. pylori infection to promote gastric cancer development. Obesity is a significant risk factor for gastric cardia adenocarcinoma, as it can promote GERD and Barrett's esophagus, which are precursors to adenocarcinoma. Other risk factors include radiation, pernicious anemia, blood type A, prior gastric surgery for benign conditions, and Epstein-Barr virus. A positive family history is also a significant risk factor, particularly with genetic syndromes such as hereditary nonpolyposis colon cancer and Li-Fraumeni syndrome. Prevention strategies include lifestyle modifications, such as reducing salt and nitrite intake, increasing fruit and vegetable consumption, and quitting smoking. H. pylori eradication therapy is a potential chemoprevention strategy, with a high cure rate and durable responses. Antioxidants may also play a role in preventing gastric cancer, although their effectiveness varies. COX-2 inhibitors may provide a chemopreventive strategy against gastric carcinogenesis. Endoscopic screening and surveillance are important for early detection, particularly in high-risk populations. Mass screening programs have led to a significant reduction in gastric cancer mortality in countries like Japan. Future prevention efforts should focus on modifiable risk factors in high-riskGastric cancer remains a significant global health issue, being the fourth most common cancer and the second leading cause of cancer death worldwide. Despite a decline in incidence in the US and elsewhere over the past several decades, gastric cancer incidence and mortality have varied by tumor location and histology. Distal, intestinal-type gastric cancers have declined, while proximal, diffuse-type adenocarcinomas of the gastric cardia have increased, particularly in Western countries. Incidence varies by geographic location, race, and socioeconomic status, with distal gastric cancer more common in developing countries, among blacks, and in lower socioeconomic groups, while proximal tumors are more common in developed countries, among whites, and in higher socioeconomic classes. These differing trends suggest that the two types of gastric cancer may have distinct etiologies. The main risk factors for distal gastric cancer include Helicobacter pylori (H. pylori) infection and dietary factors, while gastroesophageal reflux disease (GERD) and obesity are significant in the development of proximal stomach cancer. H. pylori infection is a major contributor to gastric cancer, with a strong association between chronic H. pylori infection and the development of gastric cancer. The prevalence of H. pylori infection is linked to socioeconomic factors, and its decline in developed countries has paralleled the decrease in gastric cancer incidence. Dietary factors such as high salt intake and low consumption of fresh fruits and vegetables are also associated with increased gastric cancer risk. H. pylori infection can facilitate the growth of nitrosating bacteria, which produce carcinogenic N-nitroso compounds. Salt-preserved foods and dietary nitrite are potentially carcinogenic and may act synergistically with H. pylori infection to promote gastric cancer development. Obesity is a significant risk factor for gastric cardia adenocarcinoma, as it can promote GERD and Barrett's esophagus, which are precursors to adenocarcinoma. Other risk factors include radiation, pernicious anemia, blood type A, prior gastric surgery for benign conditions, and Epstein-Barr virus. A positive family history is also a significant risk factor, particularly with genetic syndromes such as hereditary nonpolyposis colon cancer and Li-Fraumeni syndrome. Prevention strategies include lifestyle modifications, such as reducing salt and nitrite intake, increasing fruit and vegetable consumption, and quitting smoking. H. pylori eradication therapy is a potential chemoprevention strategy, with a high cure rate and durable responses. Antioxidants may also play a role in preventing gastric cancer, although their effectiveness varies. COX-2 inhibitors may provide a chemopreventive strategy against gastric carcinogenesis. Endoscopic screening and surveillance are important for early detection, particularly in high-risk populations. Mass screening programs have led to a significant reduction in gastric cancer mortality in countries like Japan. Future prevention efforts should focus on modifiable risk factors in high-risk