OBJECTIVE: The objective of this study is to examine hypotheses relating to the etiology and prevention of esophageal cancer and gastric cancer in the Nutrition Intervention Trials in Linxian China project. BACKGROUND: Gastric cancer and esophageal cancer are the second and sixth most common causes of cancer death worldwide. Significant reduction in their mortality will require development of new prevention strategies based on identification of modifiable risk factors. METHODS: Between 1985 and 1991, we conducted two randomized nutrition intervention trials (NIT), in Linxian, China. These trials, with a combined enrollment of nearly 33,000, evaluated the effect of supplementation with several vitamin/mineral combinations on esophageal cancer and gastric cancer and found significant reductions in total mortality and gastric cancer mortality among those taking a combination of selenium, beta-carotene and vitamin E. Since 1991, we have followed the NIT participants as a cohort, and have performed nested studies evaluating the association between baseline characteristics and later development of esophageal cancer and gastric cancer. PROGRESS: Recent results from nested studies in the NIT cohort have shown: (1) a strong association between low serum selenium levels and increased esophageal cancer and gastric cardia cancer; (2) no relation between serum carotenoids and esophageal cancer or gastric cancer; (3) a strong association between low serum alpha-tocopherol levels and increased esophageal cancer; (4) a strong association between low tissue zinc levels and increased esophageal cancer; (5) increased risk for gastric cancer, both cardia and noncardia, among subjects with positive serology for H pylori; (6) no relation between fumonisin exposure and esophageal cancer; (7) an association between tooth loss and esophageal cancer and gastric cancer; and (8) associations between several genetic polymorphisms and esophageal cancer and gastric cardia cancer.