CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC‐EURGAST study

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 μg/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. © 2006 Wiley‐Liss, Inc.

Association between Chronic Atrophic Gastritis and Serum Antibodies to 15 Helicobacter pylori Proteins Measured by Multiplex Serology

“…Besides host susceptibility and environmental factors, differences in the virulence of different H. pylori strains are supposed to be an important determinant for such diversity (25). A prominent example is CagA, which was discovered more than 10 years ago and has now been widely accepted as a relevant virulence factor (26)(27)(28)(29)(30). Similar results have been obtained for VacA, although its importance is still under debate (29,31,32).…”

The Association of Gastric Cancer Risk with Plasma Folate, Cobalamin, and Methylenetetrahydrofolate Reductase Polymorphisms in the European Prospective Investigation into Cancer and Nutrition

“…We gave preference to the genotyping results from the Barcelona laboratory in the three instances of discrepancies and for the Swedish center. Quantification of anti-Hp antibodies in stored plasma samples was done using an ELISA technique using incubation with lysates of the CCUG Hp strain (51). Pepsinogen A (PGA) was assayed in plasma by a commercial microplate-based quantitative ELISA kit (Biohit).…”

Vitamins B2 and B6 and Genetic Polymorphisms Related to One-Carbon Metabolism as Risk Factors for Gastric Adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition

“…These single-nucleotide polymorphisms (SNP) are "nonsynonymous" and are often called "potentially functional" (35). Quantification of anti-Hp (Hp) antibodies in stored plasma samples was done by an ELISA technique using incubation with lysates of the CCUG Hp strain (36). Pepsinogen A (PGA) was assayed in plasma by a commercial microplate-based quantitative ELISA kit (Biohit).…”