Helicobacter pylori and CagA seropositivity and its association with gastric and oesophageal carcinoma.

OBJECTIVE: Helicobacter pylori infection is an established risk factor for non-cardia gastric adenocarcinoma. Infection with H. pylori strains harbouring the cagA pathology island may augment this association. H. pylori infection may at the same time reduce the risk for oesophageal carcinoma. However, prospective data on the association between CagA seropositivity and gastric or oesophageal carcinomas are limited. The purpose of this study was to investigate whether CagA seropositivity among H. pylori seropositive subjects is associated with gastric or oesophageal carcinomas. MATERIAL AND METHODS: A nested case-control study was performed in the Malmö Preventive Medicine cohort consisting of 32,906 middle-aged subjects. Tumour cases were identified by the Swedish National Cancer Registry. The Western blot method Helicoblot 2.1 was used to detect H. pylori and CagA seropositivity. RESULTS: Non-cardia gastric adenocarcinoma was associated with H. pylori seropositivity, odds ratio 17.8 (95% CI: 4.2-74.8; 67 cases). The odds ratio for CagA seropositivity among H. pylori seropositive subjects was 9.7 (95% CI: 1.5-infinity). No significant associations were found between cardia gastric adenocarcinoma and H. pylori or CagA seropositivity among H. pylori seropositive subjects; odds ratios were 1.5 (95% CI: 0.51-4.8) and 2.7 (95% CI: 0.38-infinity), respectively (24 cases). Oesophageal adenocarcinoma and oesophageal squamous cell carcinoma were not significantly associated with H. pylori seropositivity or with CagA seropositivity among H. pylori seropositive subjects; the odds ratios associated with oesophageal adenocarcinoma were 0.46 (95% CI: 0.07-2.6) and 0.38 (95% CI: 0.02-24), respectively. Corresponding odds ratios for oesophageal squamous cell carcinoma were 0.44 (95% CI: 0.15-1.2; 37 cases) and 2.0 (95% CI: 0.24-infinity), respectively. CONCLUSIONS: CagA seropositivity among H. pylori seropositive subjects is a risk factor for non-cardia gastric adenocarcinoma.

Evaluation of western blot CagA seropositivity in Helicobacter pylori-seropositive and -seronegative subjects.

CagA seropositivity is an important risk factor for gastric adenocarcinoma and duodenal ulcer. However, CagA seropositivity is also found in Helicobacter pylori-seronegative subjects. Is CagA seropositivity in these subjects a sign of a past H. pylori infection, or does it represent a false-positive reaction? This study investigates the intensity of the CagA immune reaction and the variation in CagA seroprevalence with year of birth for 650 subjects belonging to the Malmo Preventive Medicine cohort. CagA and H. pylori seroprevalences were determined by Western blot analysis (Helicoblot 2.1) and enzyme-linked immunosorbent assay. The peak intensity of the CagA band was significantly lower in H. pylori-seronegative subjects than in those with concomitant H. pylori seropositivity. In H. pylori-seropositive subjects, peak CagA intensity had a bimodal distribution. The prevalence of CagA-seropositive but H. pylori-seronegative subjects increased successively and significantly with year of birth, in contrast to the prevalence of CagA-seropositive and H. pylori-seropositive subjects, which decreased significantly. However, within H. pylori-seropositive and -seronegative subgroups, CagA seroprevalences were constant for different birth cohorts. If CagA seropositivity in H. pylori-seronegative subjects represents a past H. pylori infection, there must have been some mechanisms of eradication that were more common in younger subjects and that were of more importance than the presence of gastric atrophy and the longer duration and higher prevalence of H. pylori infection found in older subjects. Antibiotic treatment of H. pylori was not common practice at the time of enrollment. On the other hand, a false-positive reaction would be constant and independent of birth cohorts, as with the H. pylori-seronegative subgroup of our study. Peak CagA intensity in H. pylori-seronegative subjects corresponded to the lower part of the bimodal distribution of peak CagA intensity in H. pylori-seropositive subjects. We conclude that a major proportion of CagA seropositivity in H. pylori-seronegative subjects represents a false-positive reaction. Peak CagA intensity has a bimodal distribution in H. pylori-seropositive subjects. Low-intensity CagA seropositivity in H. pylori-seropositive subjects is indeterminate, representing both false-positive and true-positive reactions.