Serum pepsinogen levels, Helicobacter pylori CagA Status, and cytokine gene polymorphisms associated with gastric premalignant lesions in Costa Rica.

The detection of gastric premalignant lesions, atrophic gastritis, corpus atrophic gastritis, and intestinal metaplasia, using several potential markers was examined in Costa Rica. Depending on the lesion investigated, from a total of 223 dyspeptic patients, 58 (26.0%), 31 (13.9%), or 23 (10.3%) were histologically diagnosed with atrophic gastritis, corpus atrophic gastritis, or intestinal metaplasia, respectively. Sera were used for the measurement of pepsinogen (PG) and Helicobacter pylori CagA antibody (CagA-ab) levels by ELISA, and human genomic DNAs were used for the genotyping of interleukin (IL)-1beta (-511 and +3954), IL-10 (-1082 and -592), and IL-1RN intron 2 by PCR and RFLP. Multivariate analysis was done adjusting for sex, age, and H. pylori seropositivity. Low PG levels (L-PG; PG I < or = 70 microg/L + PG I/II < or = 3), very low PG levels (VL-PG; PG I < or = 30 microg/L + PG I/II < or = 2), and CagA-ab were individually associated with all premalignant lesions whereas IL-1beta +3954T-carrier and IL-1RN homozygous 2 allele were associated with intestinal metaplasia. VL-PG, for corpus atrophic gastritis detection, was the single marker with the highest combination of test characteristics, sensitivity (77.4%), specificity (80.7%), positive predictive value (39.3%), negative predictive value (95.7%), and seropositivity rate (27.4%), expected to improve after periodic measurements. Combined examinations of VL-PG and CagA-ab improved the specificity (92.7%) and positive predictive value (62.2%), with similar sensitivity (74.2%) and negative predictive value (95.7%). In conclusion, corpus atrophic gastritis detection with periodic measurements of serum PG, alone or in combination with CagA-ab status, to identify high gastric cancer risk, seems to be the method best suited for mass screening in Costa Rica.

Helicobacter pylori CagA status associated with gastric cancer incidence rate variability in Costa Rican regions.

BACKGROUND: We evaluated several risk factors for gastric cancer in Costa Rican regions having contrasting gastric cancer incidence rates, despite the small dimensions of the country. METHODS: A total of 180 dyspeptic patients were classified into two groups according to the gastric cancer incidence (GCI) rate in their Costa Rican region: group A, with a high GCI rate (n = 91) and group B, with a low GCI rate (n = 89). Helicobacter pylori infection was detected by rapid urease test, Gram staining, and histological observation. Antral and corpus specimens were obtained to assess the grade of inflammation, topography of gastritis, gastric atrophy, and intestinal metaplasia by histological examination. Serum CagA antibody was measured by an antigen-specific enzyme-linked immunosorbent assay. RESULTS: There was no significant difference in H. pylori prevalence between groups A (73%) and B (63%); however, serum CagA antibody was more frequently detected in group A (79%) than in group B (54%) [P = 0.02; odds ratio (OR), 2.68]. Among patients under 60 years of age, serum CagA antibody was even more frequently detected in group A (81%) than in group B (49%) (P < 0.01; OR, 4.50). The prevalence of corpus-predominant gastritis, atrophic gastritis, and moderate/severe grades of neutrophilic infiltration was higher in serum CagA antibody-positive patients than in CagA antibody-negative patients (P = 0.003, 0.04, and 0.002, respectively). CONCLUSIONS: Infection with H. pylori possessing the cagA gene is associated with the development of severe gastric damage such as gastric atrophy, leading to gastric cancer, and probably influences the differences in GCI between Costa Rican regions.