Sex differences in mucosal response to Helicobacter pylori infection in the stomach and variations in interleukin‐8, COX‐2 and trefoil factor family 1 gene expression

Background: Gastric cancer incidence in men is almost double that in women. We investigated mucosal responses in the stomach against Helicobacter pylori (H. pylori) infections to elucidate the interindividual or sex-related differences, which may in turn be associated with gastric cancer incidence, mucosal changes of stomach as measured by the Sydney System, and interleukin-8, cyclooxygenase-2 and trefoil factor family 1 (TFF1) gene expression. Methods: An age-, sex-, H. pylori status- and disease-matched case-control study was performed in 574 H. pylori-positive and 225 H. pylori-negative patients selected from 4125 patients with a diagnosis of benign disease of the stomach. Levels of acute and chronic inflammations, atrophy and intestinal metaplasia scored according to the Sydney System were compared by stomach site and by sex. Two biopsy specimens (antral and corpus gastric mucosa) from patients with benign gastric diseases (142 patients; 72 men, 70 women) were analysed for interleukin-8, cyclooxygenase-2 and TFF1 mRNA expression as measured by real-time PCR. Results: Inflammation and activity scores in antrum with H. pylori infection were higher in men, but scores declined according to age. Atrophy and intestinal metaplasia scores in corpus with H. pylori infection appeared more severe in men than in women, especially in older patients. In women, atrophy score increased with increasing age, particularly in postmenopausal H. pylori-negative patients. Interleukin-8 mRNA induction was detected in both antrum and corpus mucosa in H. pylori infection, but sex differences were not found. Response of cyclooxygenase-2 mRNA expression against H. pylori infection in the mucosa was higher in men than women. In H. pylori-negative patients, TFF1 mRNA levels in women were significantly higher than in men, and TFF1 mRNA was significantly lower in positive than negative women. Conclusions: Sex differences in mucosal responses to H. pylori infection in the stomach may be correlated with sex differences in the incidence of stomach cancer.