Gastric Cancer and Premalignant Lesions in Atrophic Gastritis: A Controlled Trial on the Effect of Supplementation with Alpha-Tocopherol and Beta-Carotene

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Abstract
Vitamin E and beta-carotene are considered to decrease the risk of gastric cancer both in humans and in laboratory animals. We studied the effect of dietary supplementation with alpha-tocopherol and beta-carotene on the end-of-trial prevalence of premalignant and malignant lesions of the stomach in older men with atrophic gastritis. The study was carried out within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC study) in Finland, in which 29,133 male smokers aged 50-69 years were randomly assigned to receive daily 50 mg alpha-tocopherol, 20 mg beta-carotene, both of these agents, or placebo, for 5-8 years. Serum pepsinogen was determined at base line and after 3 years' supplementation to find men with atrophic gastritis. A low serum pepsinogen I level, indicating atrophic gastritis of the corpus area of the stomach, was found in 2132 men. These men were invited to have upper gastrointestinal endoscopy (gastroscopy), which was performed on 1344 subjects after a median supplementation time of 5.1 years. Neoplastic alterations were found in 63 of the men (4.7%): 42 with definite dysplasias of low grade (moderate dysplasia), 7 with definite dysplasias of high grade (severe dysplasia), 11 with carcinomas (of which 7 were 'early' cancers), and 3 with carcinoid tumors. Neither alpha-tocopherol (relative risk, 0.98; 95% confidence interval, 0.57-1.69) nor beta-carotene (relative risk, 1.13; 95% confidence interval, 0.65-1.95) supplementation had any association with end-of-trial prevalence of gastric neoplasias after adjustment for other possible risk factors. The effect was not modified by base-line serum level or dietary intake of vitamins, prevalence of Helicobacter pylori infection, or other covariates. We thus conclude that supplementation with alpha-tocopherol or beta-carotene for 5 years has no major impact on the occurrence of neoplastic changes of the stomach in older male smokers with atrophic gastritis.