A model for gastric cancer epidemiology

P Correa, W Haenszel, C Cuello, S Tannenbaum… - The Lancet, 1975 - Elsevier
P Correa, W Haenszel, C Cuello, S Tannenbaum, M Archer
The Lancet, 1975Elsevier
It is postulated that one major subtype of gastric carcinoma (" intestinal type") is the end-
result of a series of mutations and cell transformation begun in the first decade of life. The
mutagen could be a nitroso compound synthesised in the upper gastrointestinal tract by the
action of nitrite (ie, from food or saliva) on naturally occurring nitrogen compounds. Under
normal conditions these nitroso compounds do not reach the gastric epithelial cell,
presumably because their synthesis is inhibited by antioxidants present in food or because …
Abstract
It is postulated that one major subtype of gastric carcinoma ("intestinal type ") is the end-result of a series of mutations and cell transformation begun in the first decade of life. The mutagen could be a nitroso compound synthesised in the upper gastrointestinal tract by the action of nitrite (i.e., from food or saliva) on naturally occurring nitrogen compounds. Under normal conditions these nitroso compounds do not reach the gastric epithelial cell, presumably because their synthesis is inhibited by antioxidants present in food or because of their inability to pass the mucous barrier. The barrier may be overcome by abrasives or irritants such as hard grains, food with high sodium-chloride concentration, or surfactants. Once the first mutation occurs, the glandular gastric epithelium is gradually changed to intestinal-type epithelium, the mucous barrier altered, and the pH elevated. Under these conditions, bacteria proliferate in the gastric cavity and facilitate the conversion of nitrates to nitrites, thereby increasing the nitrite pool and the probability of formation of mutagenic-carcinogenic nitroso compounds. This process of gastric atrophy and intestinal metaplasia goes on for 30 to 50 years until some of the individuals affected have the final mutation or cell transformation which allows the cell to become autonomous and invade other tissues.
Elsevier