While the trophic effect of gastrin leading to ECL cell hyperplasia may be a necessary factor in increasing tumor development, it may not be the sole factor involved; loss or impaired expression of the tumor-suppressor gene menin (even in heterozygous subjects), dysregulation of somatostatin response genes or those regulating chromogranin A, Reg-1 protein expression, phenotype for PPI-degradation, or presence of acquired diseases such as H. pylori or auto-immune chronic gastritis, may all modify the effects of PPIs in different susceptible individuals. This evidence concerns the gene GAST and neoplasm.