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Background: Peptic ulcer epidemiology has changed considerably within the past century. The aim of this study was to assess the 11-year cumulative incidence of peptic ulcer disease and examine the relationship between ulcer incidence and psychosocial and genetic factors. Methods: A random sample of 2416 Danish adults with no history of peptic ulcer disease residing in Copenhagen County, Denmark, attended a population-based prospective cohort study in 1983 and 1994. All participants reported whether they had had an ulcer diagnosed within the observation period. Information on socio-economic factors, family history of peptic ulcer disease (PUD) and lifestyle practices was obtained from a questionnaire. Lewis blood group antigens were assessed from blood samples and Helicobacter pylori infection status was determined with an in-house IgG ELISA. Results: The overall 11-year cumulative incidence proportion of PUD was 2.9% (95% CI (2.2; 3.6)), i.e. 1.6% (95% CI (1.1; 2.1)) for duodenal ulcer, and 1.3% (95% CI (0.8; 1.7)) for gastric ulcer. Poor socio-economic status increased the risk of PUD independently of H. pylori infection (odds ratio 2.7, 95% CI (1.1; 6.1)) and accounted for 17% of all ulcer cases. High physical activity at work increased the risk of PUD in people infected with H. pylori (odds ratio 2.6, 95% CI (0.8; 8.0)). Family history of PUD or Lewis blood group antigens did not relate to ulcer incidence. Conclusions: Poor socio-economic status is an important risk factor for PUD that exerts its effect independently of H. pylori infection. Strenuous work may increase the risk of PUD in people with H. pylori infection. Genetic factors do not influence the risk of PUD in Danish adults. [ABSTRACT FROM AUTHOR]