UNIQUE GLOBAL POPULATION

Abstract

Purpose: Gastric cancer is the second leading cause of cancer with significant geographic variability. Cytokine polymorphisms (IL-IB, IL-1RA, IL-10, TNF-a) are associated with noncardia gastric adenocarcinoma in H. pylori infected patients. Multiple genotype carriage increases cancer risk. The background prevalence of polymorphisms in Europe and Asia is about 50% (IL-IB-511T: CT, <50%; TT, 4-21% and IL-10-1082A: GA, <50%; AA,28%). No previous studies have systematically evaluated host genetic, bacterial and dietary factors in a population-based study, nor polymorphisms in Latin America. Methods: We conducted aprospective, population-based, case-control study in Honduras, Central America. The western region (95% Mestizo) has a high incidence of gastric cancer, with standardized annual incidence rates of 39 and 21(M,F), often in younger patients (25%,12% under ages 50,35). Cases were enrolled at the Western Regional Hospital. Controls were selected from houses at random using mapping from the Honduran government thru UNESCO. Unique image-based software established dietary and micronutrient intake. Results: We have enrolled 258 subjects, with genetic data available for 110 controls and 65 cases(IL-1B,IL-10). The rates of high risk polymorphisms are the highest reported, defining a significant genetic risk in the Honduran population. In the controls, the IL-1B-511T+ prevalence was 84% (95% CI, 81–88%) with CT 57%, TT 27%. The IL-10-1082A+ prevalence was 93% (95% CI, 91–95%) with GA 33%, AA 60%. Endemic H. pylori infection was confirmed (88%). Nutrient data suggests antioxidant deficiencies (alphacarotene, selenium). Haplotype Analysis shows that 89% of the general population is at increased risk for gastric adenocarcinoma. Nearly 20% of the population was homozygotic for both polymorphisms (TT/AA), while less than 1% carried the wild type (CC/GG). Haplotype prevalence was increased in the cancer group, shy of statistical significance (p = 0.11), due to sample size given the high backround genotype prevalence. Conclusions: This is the first study of gastric cancer cytokine polymorphisms in Latin America and the Latino population. We have identified a unique population with endemic genetic susceptibility, defined by the highest reported prevalence of haplotypes of cytokine polymorphisms in the setting of endemic H. pylori infection. Host genetics, H. pylori, and diet explain the high incidence and provide an opportunity to design intervention studies.