title: 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 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.
authors.affiliation: Molecular and Nutritional Epidemiology Unit, CSPO, Scientific Institute of Tuscany, Florence, Italy. d.palli@cspo.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.forename: Daniela
authors.initials: D
authors.lastname: Basso
authors.forename: Duccio
authors.initials: D
authors.lastname: Berti
authors.forename: Mattijs E
authors.initials: ME
authors.lastname: Numans
authors.forename: Mattijs
authors.initials: M
authors.lastname: E Numans
authors.forename: Marco
authors.initials: M
authors.lastname: Ceroti
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno de Mesquita
authors.forename: Frederike L
authors.initials: FL
authors.lastname: Buchner
authors.forename: Francoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.forename: Calogero
authors.initials: C
authors.lastname: Saieva
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Olof
authors.initials: O
authors.lastname: Nyrén
authors.forename: Henrik
authors.initials: H
authors.lastname: Simán
authors.forename: Goran
authors.initials: G
authors.lastname: Berglund
authors.forename: Goran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Sanchez
authors.forename: Nerea
authors.initials: N
authors.lastname: Larrãnaga
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: Jose R
authors.initials: JR
authors.lastname: Quiros
authors.forename: Tim
authors.initials: T
authors.lastname: Key
authors.forename: Naomi
authors.initials: N
authors.lastname: Allen
authors.forename: Sheila
authors.initials: S
authors.lastname: Bingham
authors.forename: Kay Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weikert
authors.forename: Jakob
authors.initials: J
authors.lastname: Linseisen
authors.forename: Gabriele
authors.initials: G
authors.lastname: Nagel
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Reimar W
authors.initials: RW
authors.lastname: Thomsen
authors.forename: Anne
authors.initials: A
authors.lastname: Tjonneland
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichoupoulou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Athina
authors.initials: A
authors.lastname: Arvaniti
authors.forename: Guillem
authors.initials: G
authors.lastname: Pera
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
authors.forename: Pietro
authors.initials: P
authors.lastname: Ferrari
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nesi
authors.forename: Fatima
authors.initials: F
authors.lastname: Carneiro
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Gonzalez
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000382:microbiology*; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D002299:Cardia / Q000382:microbiology / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology*; D016480:Helicobacter pylori / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007390:International Agencies; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D013274:Stomach Neoplasms / Q000276:immunology / Q000382:microbiology*; D013997:Time Factors
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori