Helicobacter pylori in gastric cancer established by CagA immunoblot as a marker of past infection.
OBJECTIVE
Helicobacter pylori may disappear spontaneously with progressing precancerous changes and invalidate serologic studies of its association with gastric cancer. We reestimated the strength of the H. pylori-gastric cancer relationship, using both conventional immunoglobulin (Ig) G enzyme-linked immunosorbent assay (ELISA) and immunoblot (against cytotoxin-associated antigen A [CagA] antibodies that prevail longer after eradication) to detect past H. pylori exposure more relevant for time at cancer initiation.


METHODS
In our population-based case-control study, the seroprevalence among 298 gastric adenocarcinoma cases was 72% (IgG ELISA) and 91% (immunoblot) vs. 55% and 56% among 244 controls frequency-matched for age and gender.


RESULTS
Using IgG ELISA only, the adjusted OR for noncardia gastric cancer among H. pylori-positive subjects was 2.2 (95% confidence interval [CI], 1.4-3.6). When ELISA-/CagA+ subjects (odds ratio [OR], 68.0) were removed from the reference, the OR rose to 21.0 (95% CI, 8.3-53.4) and the previous effect modification by age disappeared. ELISA+/CagA- subjects had an OR of 5.0 (95% CI, 1.1-23.6). There were no associations with cardia cancer.


CONCLUSIONS
The weaker H. pylori-cancer relationships in studies based on IgG ELISA rather than CagA may be caused by misclassification of relevant exposure. A much stronger relationship emerges with more accurate exposure classification. In the general Swedish population, 71% of noncardia adenocarcinomas were attributable to H. pylori.
Ekström
A M
AM
Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden. Anna.Mia.Ekstrom@phs.ki.se
Held
M
M
Hansson
L E
LE
Engstrand
L
L
Nyrén
O
O
D000230:Adenocarcinoma / Q000382:microbiology* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000032:analysis*; D001426:Bacterial Proteins / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016481:Helicobacter Infections / Q000453:epidemiology*; D016480:Helicobacter pylori; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000032:analysis; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D015995:Prevalence; D012016:Reference Values; D013274:Stomach Neoplasms / Q000145:classification / Q000382:microbiology* / Q000473:pathology; D013548:Sweden / Q000453:epidemiology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; C080866:cagA protein, Helicobacter pylori