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CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC-EURGAST study
Authors:Palli Domenico  Masala Giovanna  Del Giudice Giuseppe  Plebani Mario  Basso Daniela  Berti Duccio  Numans Mattijs E  E Numans Mattijs  Ceroti Marco  Peeters Petra H M  Bueno de Mesquita H Bas  Buchner Frederike L  Clavel-Chapelon Francoise  Boutron-Ruault Marie-Christine  Krogh Vittorio  Saieva Calogero  Vineis Paolo  Panico Salvatore  Tumino Rosario  Nyrén Olof  Simán Henrik  Berglund Goran  Hallmans Goran  Sanchez Maria-Jose  Larrãnaga Nerea  Barricarte Aurelio  Navarro Carmen  Quiros Jose R  Key Tim  Allen Naomi  Bingham Sheila  Khaw Kay Tee  Boeing Heiner  Weikert Cornelia  Linseisen Jakob  Nagel Gabriele  Overvad Kim
Affiliation:Molecular and Nutritional Epidemiology Unit, CSPO, Scientific Institute of Tuscany, Florence, Italy. d.palli@cspo.it
Abstract:Helicobacter pylori (H. pylori), atrophic gastritis, dietary and life-style factors have been associated with gastric cancer (GC). These factors have been evaluated in a large case-control study nested in the European Prospective Investigation into Cancer and Nutrition carried out in 9 countries, including the Mediterranean area. Participants, enrolled in 1992-1998, provided life-style and dietary information and a blood sample (360,000; mean follow-up: 6.1 years). For 233 GC cases diagnosed after enrolment and their 910 controls individually-matched by center, gender, age and blood donation date H. pylori antibodies (antilysate and antiCagA) and plasma Pepsinogen A (PGA) were measured by ELISA methods. Severe chronic atrophic gastritis (SCAG) was defined as PGA circulating levels <22 microg/l. Overall, in a conditional logistic regression analysis adjusted for education, smoke, weight and consumption of total vegetables, fruit, red and preserved meat, H. pylori seropositivity was associated with GC risk. Subjects showing only antibodies anti-H. pylori lysate, however, were not at increased risk, while those with antiCagA antibodies had a 3.4-fold increased risk. Overall, the odds ratio associated with SCAG was 3.3 (95% CI 2.2-5.2). According to site, the risk of noncardia GC associated with CagA seropositivity showed a further increase (OR 6.5; 95% CI 3.3-12.6); on the other hand, a ten-fold increased risk of cardia GC was associated with SCAG (OR 11.0; 95% CI 3.0-40.9). These results support the causal relationship between H. pylori CagA+ strains infection, and GC in these European populations even after taking into account dietary habits. This association was limited to distal GC, while serologically defined SCAG was strongly associated with cardia GC, thus suggesting a divergent risk pattern for these 2 sites.
Keywords:Helicobacter pylori  stomach cancer  epidemiology  pepsinogen  chronic atrophic gastritis
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