Association of helicobacter pylori infection and chronic atrophic gastritis with risk of colonic, pancreatic and gastric cancer: A ten-year follow-up of the ESTHER cohort study.

Felipe Andres Castro,Hermann Brenner,Ben Schöttker,Bernd Holleczek,Xin-Zu Chen,Hongda Chen,Yan Zhang

doi:10.18632/oncotarget.7946

Abstract

ObjectivesTo assess the association of H. pylori and chronic atrophic gastritis (AG) with colonic, pancreatic and gastric cancer in a population-based prospective cohort.MethodsSerum antibodies against H. pylori in general and specific to cytotoxin-associated gene A (CagA), as well as serum pepsinogen I and II were analyzed in 9,506 men and women, aged 50–75 years in a cohort study from Saarland, Germany. Incident cases of colonic, pancreatic and gastric cancer were ascertained by record linkage with data from the Saarland Cancer Registry.ResultsDuring an average follow-up of 10.6 years, 108 colonic, 46 pancreatic and 27 gastric incident cancers were recorded. There was no association between H. pylori infection and colonic cancer (HR = 1.07; 95% CI 0.73–1.56) or pancreatic cancer (HR = 1.32; 0.73–2.39), regardless of either CagA seropositivity or AG status. In contrast, CagA+ infection was associated with a strongly increased risk of gastric cancer, especially non-cardia gastric cancer, and this association was particularly pronounced in the presence of AG. Compared to people without AG and without CagA+ infection, people with both risk factors had a significantly increased risk of non-cardia gastric cancer (HR = 32.4; 7.6–137.6).ConclusionsThis large cohort study did not observe an association of H. pylori infection or AG with colonic or pancreatic cancer, but underlines that the vast majority of non-cardia gastric cancers arise from AG and infection with CagA+ H. pylori strains.

Highlights

Helicobacter pylori (H. pylori) is well-known as a carcinogenic pathogen for gastric cancer [1]
H. pylori infection shows a strong association with chronic atrophic gastritis (AG), which is considered as a precancerous lesion of the gastric mucosa [7]
Gastric cancer incidence was much higher among participants infected with cytotoxin-associated gene A (CagA)+ H. pylori strains than among those infected with CagA– H. pylori strains

Summary

Introduction

Helicobacter pylori (H. pylori) is well-known as a carcinogenic pathogen for gastric cancer [1]. H. pylori infection is likely to be primarily involved in the early stage of development of AG, and less so in the development of gastric cancer from AG [8]. The 4th European Helicobacter Study Group’s Maastricht IV/Florence Consensus Report stated that the www.impactjournals.com/oncotarget combination of H. pylori infection and AG determined by serological examination is suiTable for the identification of subjects with a high risk of gastric cancer [10]. The European Helicobacter Study Group recommends that differences in H. pylori virulence factors shall be taken into account to identify subjects with high risk of gastric cancer because the oncogenic potential of H. pylori infections strongly varies according to the presence of virulent strains [10]. The cytotoxin-associated gene A (CagA) strain is thought to contribute to cancer development by steps from inflammation to atrophy and cancer [11,12,13]

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