Helicobacter pylori but not gastrin is associated with the development of colonic neoplasms Michael Selgrad 1 , Jan Bornschein 1 , Arne Kandulski 1 , Carla Hille 1 , Jochen Weigt 1 , Albert Roessner 2 , Thomas Wex 1,3 and Peter Malfertheiner 1 1 Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Magdeburg, Germany 2 Department of Pathology, Otto-von-Guericke-University of Magdeburg, Magdeburg, Germany 3 Medical Laboratory for Clinical Chemistry, Microbiology and Infectious Diseases, Department of Molecular Genetics, Magdeburg, Germany Recent studies have suggested that Helicobacter pylori (H. pylori) constitutes a risk for the development of colonic neoplasia. Hypergastrinemia can be induced by H. pylori infection, and gastrin can act as putative promoter of colorectal carcinogenesis. Aim of our study was to assess whether H. pylori infection and/or increased serum gastrin levels are associated with the occurrence of colonic neoplasms. For this, we reviewed prospectively collected data of 377 patients with a minimum age of 50 years who underwent colonoscopy. H. pylori and CagA status were determined by serology. Serum gastrin levels were measured in fasting state by commercially available assay. In H. pylori infected patients (n 5 138; 36.6%), the overall preva- lence of colonic neoplasms was more frequent compared to H. pylori negative patients (n 5 239; 63.4%) (OR 5 2.73, 95% CI: 1.76–4.24). H. pylori infection occurred more frequently in patients with hyperplastic polyps (OR 5 2.66, 95% CI: 1.23–5.74) and adenomas presenting with low grade intraepithelial neoplasia (IEN) (OR 5 1.85, 95% CI: 1.14–2.99). Attributable risk for adenomas with high grade IEN and colorectal adenocarcinoma (n 5 14) was not assessed due to the low number of cases. The expression of CagA was also associated with an increased risk for colonic neoplasms (OR 5 2.25, 95% CI: 1.29–3.94). Hyper- gastrinemia did not increase the risk for any colonic neoplasms and there was no difference in basal serum gastrin levels between H. pylori positive and negative patients. In conclusion, H. pylori infection, including CagA expression is associated with an increased risk for the development of colonic neoplasm. Helicobacter pylori (H. pylori) infection affects 20–50% of the adult population in industrialized nations and remains a sig- nificant cause of morbidity and mortality in gastro-duodenal diseases. 1,2 H. pylori infection is the main risk factor for the development of adenocarcinoma of the stomach 3,4 and pre- disposes to several other complications that include peptic ulcer disease and mucosa-associated lymphoid tissue lym- phoma. Among bacterial virulence factors of H. pylori that are responsible for an increase in pathogenicity of the bacte- ria, CagA plays a prominent role. CagA is not expressed in all H. pylori strains, but CagA positive H. pylori strains show an association with higher grades of inflammation of the gas- tric mucosa and significantly increase the risk of gastric can- cer development. 5,6 Moreover, H. pylori infection has been suggested to also play a role in extragastric malignancies. 7 In this context, previous studies have demonstrated that H. pylori infection is associated with an increased risk for the development of colonic neoplasms. 8–13 Most of the studies have used positive serology for anti-H. pylori antibodies as a marker for H. pylori infection. But a recent study has further strengthened the association by showing that various forms of H. pylori-induced gastritis display an attributable risk for the occurrence of colorectal neoplasms. 8 The pathophysiolog- ical mechanism underlying the association between H. pylori infection and colorectal neoplasms is unclear and certainly not explained by a direct effect of H. pylori, since H. pylori is uniquely adapted to colonize the gastric mucosa. 7 A hypothe- sis is that H. pylori may contribute to the colonic carcinogen- esis indirectly via gastrin: H. pylori-induced atrophic changes of the gastric body mucosa lead to increased levels of serum gastrin by negative feedback on the antral G-cells. 14 Gastrin is capable of stimulating growth factor dependent signaling pathways and therefore hypergastrinemia may act as a puta- tive promoter of colorectal neoplasia in humans. 15 In vitro, high gastrin levels have been shown to be associated with growth and proliferation of colon cancer cells. 16,17 Further- more, patients with elevated gastrin levels (i.e., Zollinger- Key words: Helicobacter pylori, gastrin, colonic neoplasms Grant sponsor: BMBF; Grant number: BMBF-0315905D (in the frame of ERA-NET PathoGenoMics) DOI: 10.1002/ijc.28758 History: Received 10 July 2013; Accepted 20 Jan 2014; Online 4 Feb 2014 Correspondence to: Michael Selgrad, Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von- Guericke-University of Magdeburg, Leipziger Str. 44, D-39120 Mag- deburg, Germany, Tel.: 149-391-6713100, Fax: 149-391-6713105, E-mail: michael.selgrad@med.ovgu.de or Peter Malfertheiner, Depart- ment of Gastroenterology, Hepatology and Infectious Diseases, Otto- von-Guericke-University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany. Infectious Causes of Cancer Int. J. Cancer: 135, 1127–1131 (2014) V C 2014 UICC International Journal of Cancer IJC