Mechanisms for the Sex-Specific Effect of H. Pylori on Risk of Gastroesophageal Reflux Disease and Barrett’s Esophagus

Abstract

Background: Mechanisms for how Helicobacter pylori infection respectively. No association was observed for women. H. pylori-affects risk of gastroesophageal reflux disease (GERD) and Barrett’s induced atrophic antral gastritis was more common in men (68%) esophagus are incompletely understood and might differ by sex. than in women (56%; P ¼ 0.015). For men, 5 of the 15 per 1,000 Methods: In a case–control study nested in the Melbourne excess Barrett’s esophagus risk from being seronegative were mediCollaborative Cohort Study with 425 GERD cases and 169 Barrett’s ated by GERD. esophagus cases (identified at 2007–2010 follow-up), we estimated Conclusions: Men, but not women, who were H. pylori serosex-specific odds ratios for participants who were H. pylori seronegative had increased risks of GERD and Barrett’s esophagus. A negative versus seropositive at baseline (1990–1994). To explore possible explanation might be sex differences in patterns of possible mechanisms, we (i) compared patterns of H. pylori-induced H. pylori-induced atrophic antral gastritis, which could lead to less gastritis by sex using serum pepsinogen-I and gastrin-17 data and erosive reflux for men. Evidence of GERD mediating the effect of (ii) quantified the effect of H. pylori seronegativity on Barrett’s H. pylori on Barrett’s esophagus risk among men supports this esophagus mediated by GERD using causal mediation analysis. proposed mechanism. Results: For men, H. pylori seronegativity was associated with Impact: The findings highlight the importance of investigating 1.69-fold [95% confidence interval (CI), 1.03–2.75] and 2.28-fold sex differences in the effect of H. pylori on risk of GERD and (95% CI, 1.27–4.12) higher odds of GERD and Barrett’s esophagus, Barrett’s esophagus in future studies.