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Serum Pepsinogen Levels, Helicobacter pylori CagA Status, and Cytokine Gene Polymorphisms Associated with Gastric Premalignant Lesions in Costa Rica

¹ Centro Digestivo Doctores Con-Mediplaza; ² Laboratorio Clínico Echandi-Mediplaza; ³ Laboratorio de Patología-Mediplaza, Pavas, San José, Costa Rica; and Departments of ⁴ Tumor Surgery, ⁵ Clinical Laboratory Medicine, and ⁶ Public Health, Kochi Medical School, Kochi University, Nankoku-city, Kochi, Japan

Requests for reprints: Sergio A. Con, Department of Clinical Laboratory Medicine, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku-city, Kochi 783-8505, Japan. Phone: 81-88-880-2427; Fax: 81-88-880-2428. E-mail: scon{at}gastrocolon.com

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)-1β (–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 70 µg/L + PG I/II 3), very low PG levels (VL-PG; PG I 30 µg/L + PG I/II 2), and CagA-ab were individually associated with all premalignant lesions whereas IL-1β +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)