Is the association between Helicobacter pylori and gastric cancer confined to CagA-positive strains?
BACKGROUND
Infection with Helicobacter pylori is associated with an increased risk of gastric cancer. Several studies have indicated that the association differs with strain type. We aimed to find out if infection with strains lacking the virulence factor CagA is linked to gastric cancer risk.


METHODS
In a hospital-based case-control study, we collected sera from 100 case patients with a newly diagnosed gastric adenocarcinoma and 96 control patients with diseases unrelated to H. pylori status. Antibodies to H. pylori were analyzed by enzyme-linked immunosorbent assay (ELISA), and antibodies to CagA were detected by immunoblot. Logistic regression was used to obtain odds ratios (ORs) as estimates of relative risk, adjusted for potential confounding.


RESULTS
Among the case patients, 81% were ELISA positive and 86% had antibodies to CagA. The corresponding numbers among the controls were 58% and 55%, respectively. ELISA positivity was associated with an increased risk of gastric adenocarcinoma compared to ELISA negativity (OR for gastric cancer regardless of site 3.9, 95% CI 1.9-8.2). The OR was 7.4 (95% CI 3.3-16.6) for CagA-positive relative to CagA-negative subjects. Among ELISA-positive subjects the presence of CagA antibodies increased the risk 3.6 times (95% CI 1.2-11.1). ELISA-positive CagA-negative infections were associated with a fourfold increased risk (OR = 4.2, 95% CI 1.0-17.0) compared to no infection (ELISA-negative and CagA-negative).


CONCLUSIONS
Although patients with antibodies to CagA have the greatest risk of developing gastric cancer, those with CagA-negative infections run a significantly greater risk than uninfected persons.
Held
Maria
M
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Engstrand
Lars
L
Hansson
Lars-Erik
LE
Bergström
Reinhold
R
Wadström
Torkel
T
Nyrén
Olof
O
D000230:Adenocarcinoma / Q000453:epidemiology* / Q000382:microbiology; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D016481:Helicobacter Infections / Q000150:complications* / Q000453:epidemiology / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006761:Hospitals; D006801:Humans; D008297:Male; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000382:microbiology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori