CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC-EURGAST study.
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.
Palli
Domenico
D
Molecular and Nutritional Epidemiology Unit, CSPO, Scientific Institute of Tuscany, Florence, Italy. d.palli@cspo.it
Masala
Giovanna
G
Del Giudice
Giuseppe
G
Plebani
Mario
M
Basso
Daniela
D
Berti
Duccio
D
Numans
Mattijs E
ME
E Numans
Mattijs
M
Ceroti
Marco
M
Peeters
Petra H M
PH
Bueno de Mesquita
H Bas
HB
Buchner
Frederike L
FL
Clavel-Chapelon
Francoise
F
Boutron-Ruault
Marie-Christine
MC
Krogh
Vittorio
V
Saieva
Calogero
C
Vineis
Paolo
P
Panico
Salvatore
S
Tumino
Rosario
R
Nyrén
Olof
O
Simán
Henrik
H
Berglund
Goran
G
Hallmans
Goran
G
Sanchez
Maria-Jose
MJ
Larrãnaga
Nerea
N
Barricarte
Aurelio
A
Navarro
Carmen
C
Quiros
Jose R
JR
Key
Tim
T
Allen
Naomi
N
Bingham
Sheila
S
Khaw
Kay Tee
KT
Boeing
Heiner
H
Weikert
Cornelia
C
Linseisen
Jakob
J
Nagel
Gabriele
G
Overvad
Kim
K
Thomsen
Reimar W
RW
Tjonneland
Anne
A
Olsen
Anja
A
Trichoupoulou
Antonia
A
Trichopoulos
Dimitrios
D
Arvaniti
Athina
A
Pera
Guillem
G
Kaaks
Rudolf
R
Jenab
Mazda
M
Ferrari
Pietro
P
Nesi
Gabriella
G
Carneiro
Fatima
F
Riboli
Elio
E
Gonzalez
Carlos A
CA
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
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori