Between 1985 and 1991, approximately 30,000 persons in Linxian, China participated in two nutritional intervention trials that tested whether various mineral and vitamin supplements would decrease the incidence of esophageal and gastric cancer. In 1996, the mortality and morbidity of these participants was assessed by interview, physical examination, and some endoscopic examinations. During this first five years post intervention there were 1,388 new incident esophageal and gastric cancers, and 1,158 new strokes. Analyses of these data show: 1) the benefits on overall mortality found in the group who received selenium, beta-carotene, and vitamin E during the course of the General Population trial have persisted five years after the end of intervention; 2) the small but statistically insignificant benefit of a multivitamin on esophageal cancer in the Dysplasia Trial has increased ; 3) there are statistically significant benefits on cancer mortality for both the multivitamin and the selenium, beta-carotene, vitamin E supplement for participants less than 55 years old. We are currently analyzing these results at 10 years post intervention. We have also conducted several studies examining the relationship between serum levels of minerals and vitamins before the supplements were given, and the subsequent risk of developing squamous esophageal, gastric cardia, and gastric non-cardia cancers. In particular we have examined the associations of the three nutrients most implicated by the trial as being related to cancer incidence. The most striking results have been a finding of a dose dependent decrease in esophageal and gastric cardia cancer with increasing levels of selenium and alpha-tocopherol. No such relationship was seen with beta-carotene. We have used similar studies to evaluate the association of B vitamins, cysteine, and homocysteine with these cancers. We have found a significant inverse association of serum cysteine with the incidence of esophageal and gastric cardia cancers, and a significant inverse association of serum riboflavin with esophageal cancer. Gastric cancer is the second most frequent cause of death from cancer in the world and the leading cause of death from cancer in China, In September 1995, we launched a randomized multi-intervention trial to inhibit the progression of precancerous gastric lesions in Linqu County, Shandong Province, an area of China with one of the world's highest rates of gastric cancer. Treatment compliance was measured by pill counts and quarterly serum concentrations of vitamin C, vitamin E and S-allyl cysteine, In 1999, toxicity information was collected from each trial participant to evaluate treatment-related side-effects during the trial, and endoscopies were performed on 92% of the originally randomized subjects. A final endoscopy after 7.5 years of intervention is scheduled for March, 2003. Compliance rates to taking vitamin and garlic supplements have consistently exceeded 90%. No significant differences in side-effects were observed between the placebo treatment group and the vitamins/mineral and garlic preparation treatment.
