NUTRITION INTERVENTION TRIALS IN LINXIAN, CHINA - MULTIPLE VITAMIN MINERAL SUPPLEMENTATION, CANCER INCIDENCE, AND DISEASE-SPECIFIC MORTALITY AMONG ADULTS WITH ESOPHAGEAL DYSPLASIA

Background: A number of vitamins and minerals have been shown to influ ence carcinogenesis in experimental animals. In humans, epidemiologic evidence suggests that intake of fruits and vegetables may reduce risk of esophageal and other cancers. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian, Chi na, have persistently low intake of multiple nutrients and exhibit one of the world's highest rates of esophageal/gastric cardia cancer, wit h an exceptionally high risk of esophageal dysplasia. Purpose: To dete rmine whether supplementation with multiple vitamins and minerals may reduce esophageal/gastric cardia cancer among persons with esophageal dysplasia, we conducted a 6-year prospective intervention trial in Lin xian. Methods: Mortality and cancer incidence were ascertained from Ma y 1985 through May 1991 for 3318 persons with cytologic evidence of es ophageal dysplasia who were randomly assigned to receive, throughout t hat period, daily supplementation with 14 vitamins and 12 minerals or placebo. Doses were typically two to three times U.S. Recommended Dail y Allowances. Compliance was assessed by counting unused pills monthly for all trial participants and by assaying nutrient levels in blood c ollected from samples of individuals randomly selected without replace ment every 3 months throughout the trial. Cancers were identified thro ugh routine surveillance and by special cytology and endoscopy screeni ngs after 21/2 years and 6 years. Results: A total of 324 deaths occur red during the 6-year intervention period; 167 occurred in the control (placebo) group and 157 occurred in the supplement group. Cancer was the leading cause of death (54% of all deaths); 18% were due to cerebr ovascular diseases and 29% to other causes. Cumulative esophageal/gast ric cardia death rates were 8% lower (relative risk [RR] = 0.92; 95% c onfidence interval [CI] = 0.67-1.28) among individuals receiving suppl ements rather than placebo, a nonsignificant (P>.10) difference. Risk of total mortality was 7% lower (RR = 0.93; 95% CI = 0.75-1.16; P>.10) , total cancer 4% lower (RR = 0.96; 95% CI = 0.71-1.29; P>.10), cerebr ovascular disease 38% lower (RR = 0.62; 95% CI = 0.37-1.06; P = .08), and other diseases 12% higher (RR = 1.12; 95% CI = 0.74-1.69; P>.10) a mong the treated group. Cumulative cancer incidence rates were nearly the same in the two groups. Conclusions: No substantial short-term ben eficial effect on incidence or mortality for this type of cancer occur red following daily supplementation with multiple vitamins and mineral s among adults with precancerous lesions of the esophagus. Implication s: Although no statistically significant short-term benefits were obse rved, longer follow-up should be more informative about the effectiven ess of this 6-year supplementation on cancer and other diseases among individuals with esophageal dysplasia.