AIM:To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS:According to GCIR, 191 Helicobacter pylori (H pylori )-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1β and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA , vacA and babA2 . Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS:Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1β+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2,. C O N C L U S I O N :A l t h o u g h a p r o i n f l a m m a t o r y cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability 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)-1B (À511 and +3954), IL-10 (À1082 and À592), 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 V70 Mg/L + PG I/II V3), very low PG levels (VL-PG; PG I V30 Mg/L + PG I/II V2), and CagA-ab were individually associated with all premalignant lesions whereas IL-1B +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. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2631 -6)

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.

The prevalence status of the cagA and vacA (s1/m1) genes in Costa Rica seems to fall between that found in European/North American and East Asian countries, and both cagA and vacA seem to have clinical relevance in this country.