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Helicobacter pylori Infection Is Strongly Associated With Gastric and Duodenal Ulcers in a Large Prospective Study

Published:January 10, 2012DOI:https://doi.org/10.1016/j.cgh.2011.12.036

      Background & aims

      Infection with Helicobacter pylori (H pylori) is a risk factor for peptic ulcer disease (PUD), but there are limited longitudinal data on the associations between infection and incident gastric or duodenal ulcers.

      Methods

      Information on potential risk factors, lifetime history of PUD, and serologic measurements of H pylori infection were obtained from a German cohort of 9953 adults, 50 to 74 years old at baseline (2000–2002). The incidence of ulcers was determined by questionnaires sent to study participants and general practitioners 2 and 5 years later, and was validated by medical records.

      Results

      A lifetime history of PUD was reported by 1030 participants, and during the follow-up period 48 had a first gastric and 22 had a first duodenal ulcer. Infection with H pylori strains that express cytotoxin-associated gene A (cagA) was significantly associated with a lifetime history of PUD (odds ratio, 1.75; 95% confidence interval [CI], 1.50–2.04). Based on longitudinal analyses with physician-validated end points, the adjusted hazard ratios for incident gastric and duodenal ulcer disease were 2.9 (95% CI, 1.5–5.5) and 18.4 (95% CI, 4.2–79.9), respectively, among patients infected with cagA-positive strains of H pylori.

      Conclusions

      In cross-sectional analysis, infection with cagA-positive strains of H pylori was associated with a 1.75-fold increased risk of peptic ulcer disease. Longitudinal analyses revealed an 18.4- and 2.9-fold increased risk for duodenal ulcer and gastric ulcer, respectively. The proportion of PUD that is attributable to H pylori infection might be larger than previously believed.

      Keywords

      Abbreviations used in this paper:

      cagA (cytotoxin associated gene A), CI (confidence interval), ELISA (enzyme-linked immunosorbent assay), HR (hazard ratio), IR (incidence rate), NSAID (nonsteroidal anti-inflammatory drug), OR (odds ratio), PG (pepsinogen), PUD (peptic ulcer disease), PY (person-years)
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      References

        • Sung J.J.
        • Kuipers E.J.
        • El-Serag H.B.
        Systematic review: the global incidence and prevalence of peptic ulcer disease.
        Aliment Pharmacol Ther. 2009; 29: 938-946
        • Wang Y.R.
        • Richter J.E.
        • Dempsey D.T.
        Trends and outcomes of hospitalizations for peptic ulcer disease in the United States, 1993 to 2006.
        Ann Surg. 2010; 251: 51-58
        • Cai S.
        • García Rodríguez L.A.
        • Massó-González E.L.
        • et al.
        Uncomplicated peptic ulcer in the UK: trends from 1997 to 2005.
        Aliment Pharmacol Ther. 2009; 30: 1039-1048
        • Groenen M.J.
        • Kuipers E.J.
        • Hansen B.E.
        • et al.
        Incidence of duodenal ulcers and gastric ulcers in a Western population: back to where it started.
        Can J Gastroenterol. 2009; 23: 604-608
        • Barkun A.
        • Leontiadis G.
        Systematic review of the symptom burden, quality of life impairment and costs associated with peptic ulcer disease.
        Am J Med. 2010; 123: 358-366
        • Andersen I.B.
        • Bonnevie O.
        • Jørgensen T.
        • et al.
        Time trends for peptic ulcer disease in Denmark, 1981–1993.
        Scand J Gastroenterol. 1998; 33: 260-266
        • Yuan Y.H.
        • Wang C.
        • Yuan Y.
        • et al.
        Meta-analysis: incidence of endoscopic gastric and duodenal ulcers in placebo arms of randomized placebo-controlled NSAID trials.
        Aliment Pharmacol Ther. 2009; 30: 197-209
        • Papatheodoridis G.V.
        • Sougioultzis S.
        • Archimandritis A.J.
        Effects of Helicobacter pylori and nonsteroidal anti-inflammatory drugs on peptic ulcer disease: a systematic review.
        Clin Gastroenterol Hepatol. 2006; 4: 130-142
        • Huang J.Q.
        • Sridhar S.
        • Hunt R.H.
        Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis.
        Lancet. 2002; 359: 14-22
        • Rosenstock S.
        • Jørgensen T.
        • Bonnevie O.
        • et al.
        Risk factors for peptic ulcer disease: a population based prospective cohort study comprising 2416 Danish adults.
        Gut. 2003; 52: 186-193
        • Seppälä K.
        • Pikkarainen P.
        • Sipponen P.
        • et al.
        Cure of peptic gastric ulcer associated with eradication of Helicobacter pylori.
        Gut. 1995; 36: 834-837
        • Rauws E.A.
        • Tytgat G.N.
        Cure of duodenal ulcer associated with eradication of Helicobacter pylori.
        Lancet. 1990; 335: 1233-1235
        • Löw M.
        • Stegmaier C.
        • Ziegler H.
        • et al.
        [Epidemiological investigations of the chances of preventing, recognizing early and optimally treating chronic diseases in an elderly population (ESTHER study)].
        Dtsch Med Wochenschr. 2004; 129 ([in German]): 2643-2647
        • Weck M.N.
        • Stegmaier C.
        • Rothenbacher D.
        • et al.
        Epidemiology of chronic atrophic gastritis: population-based study among 9444 older adults from Germany.
        Aliment Pharmacol Ther. 2007; 26: 879-887
        • Brenner H.
        • Rothenbacher D.
        • Weck M.N.
        Epidemiologic findings on serologically defined chronic atrophic gastritis strongly depend on the choice of the cutoff-value.
        Int J Cancer. 2007; 121: 2782-2786
        • Gao L.
        • Weck M.N.
        • Stegmaier C.
        • et al.
        Alcohol consumption and chronic atrophic gastritis: population-based study among 9,444 older adults from Germany.
        Int J Cancer. 2009; 125: 2918-2922
        • Adamu M.A.
        • Weck M.N.
        • Rothenbacher D.
        • et al.
        Incidence and risk factors for the development of chronic atrophic gastritis: five year follow-up of a population-based cohort study.
        Int J Cancer. 2011; 128: 1652-1658
        • Miki K.
        • Urita Y.
        Using serum pepsinogens wisely in a clinical practice.
        J Dig Dis. 2007; 8: 8-14
        • Kato I.
        • Nomura A.M.
        • Stemmermann G.N.
        • et al.
        A prospective study of gastric and duodenal ulcer and its relation to smoking, alcohol, and diet.
        Am J Epidemiol. 1992; 135: 521-530
        • Johnsen R.
        • Førde O.H.
        • Straume B.
        • et al.
        Aetiology of peptic ulcer: a prospective population study in Norway.
        J Epidemiol Community Health. 1994; 48: 156-160
        • García Rodríguez L.A.
        • Hernández-Díaz S.
        Risk of uncomplicated peptic ulcer among users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs.
        Am J Epidemiol. 2004; 159: 23-31
        • Malfertheiner P.
        • Chan F.K.
        • McColl K.E.
        Peptic ulcer disease.
        Lancet. 2009; 374: 1449-1461
        • Mattar R.
        • Marques S.B.
        • Monteiro Mdo S.
        • et al.
        Helicobacter pylori cag pathogenicity island genes: clinical relevance for peptic ulcer disease development in Brazil.
        J Med Microbiol. 2007; 56: 9-14
        • Panayotopoulou E.G.
        • Sgouras D.N.
        • Papadakos K.S.
        • et al.
        CagA and VacA polymorphisms are associated with distinct pathological features in Helicobacter pylori-infected adults with peptic ulcer and non-peptic ulcer disease.
        J Clin Microbiol. 2010; 48: 2237-2239
        • Shiota S.
        • Matsunari O.
        • Watada M.
        • et al.
        Systematic review and meta-analysis: the relationship between the Helicobacter pylori dupA gene and clinical outcomes.
        Gut Pathog. 2010; 2: 13
        • Gao L.
        • Nieters A.
        • Brenner H.
        Cell proliferation-related genetic polymorphisms and gastric cancer risk: systematic review and meta-analysis.
        Eur J Hum Genet. 2009; 17: 1658-1667
        • Gao L.
        • Weck M.N.
        • Michel A.
        • et al.
        Association between chronic atrophic gastritis and serum antibodies to 15 Helicobacter pylori proteins measured by multiplex serology.
        Cancer Res. 2009; 69: 2973-2980
        • Gao L.
        • Michel A.
        • Weck M.N.
        • et al.
        Helicobacter pylori infection and gastric cancer risk: evaluation of 15 H. pylori proteins determined by novel multiplex serology.
        Cancer Res. 2009; 69: 6164-6170
        • Weyermann M.
        • Rothenbacher D.
        • Brenner H.
        Acquisition of Helicobacter pylori infection in early childhood: independent contributions of infected mothers, fathers, and siblings.
        Am J Gastroenterol. 2009; 104: 182-189
        • Levenstein S.
        • Kaplan G.A.
        Socioeconomic status and ulcer.
        J Clin Gastroenterol. 1998; 26: 14-17
        • Vaira D.
        • Holton J.
        • Menegatti M.
        • et al.
        Blood tests in the management of Helicobacter pylori infection.
        Gut. 1998; 43: S39-S46