Altered expression and allelic association of the hypervariable membrane mucin MUC1 in Helicobacter pylori gastritis

Background & Aims: Infection with Helicobacter pylori causes chronic gastritis, and this confers a risk of gastric cancer. Short alleles of the membrane-bound mucin MUC1, which has a large extracellular highly glycosylated domain and is highly polymorphic due to variation in the number of tandemly repeated (TR) 20–amino acid units, have been shown to be associated with gastric cancer. Our aim was to investigate the involvement of MUC1 in chronic gastritis and, by implication, gastric cancer. Methods: Immunohistochemical analysis was performed on endoscopic biopsy specimens from 95 patients. Gastritis was classified using the Sydney System, and H. pylori status was determined. MUC1 was detected with antibodies against different epitopes of the TR region and the cytoplasmic tail. Southern blot analysis of the MUC1 gene was performed on 57 Northern European patients to determine TR allele lengths. Results: With the TR antibodies, apical staining and some perinuclear staining was seen in 34 of 41 biopsy specimens classified as histologically normal and H. pylori negative. None of the 36 biopsy specimens with gastritis and current H. pylori infection showed apical staining. In contrast, the cytoplasmic tail antibody detected apical staining in both groups. Comparison of the MUC1 allele length distributions between Northern European patients with H. pylori infection and those without H. pylori gastritis showed a statistically significant difference in distribution, with shorter alleles associated with H. pylori gastritis. Conclusions: Our results suggest that H. pylori interacts with MUC1 and that there are functional allelic differences that affect susceptibility to gastritis.