Polymorphisms in Genes Coding for HSP-70 Are Associated with Gastric Cancer and Duodenal Ulcer in a Population at High Risk of Gastric Cancer in Costa Rica

Abstract

Costa Rica has among the highest incidence and mortality rates for gastric cancer worldwide. The reasons for this are largely unknown. Polymorphisms of inflammatory response genes including genes encoding heat shock proteins (HSP) have been shown to be associated with the risk of gastric cancer in some populations. This study addresses the possible association between the HSP70-2+1267 and HSP70-Hom+2437 polymorphisms and the risk of developing gastric cancer in a high-risk population in Costa Rica. DNA from 39 individuals diagnosed with gastric cancer, 79 healthy controls, 55 individuals with chronic gastritis and 52 individuals with duodenal ulcer was genotyped for the polymorphisms HSP70-2+1267 and HSP70-Hom+2437 by RFLP. Logistic regression analysis was used to determine possible associations with the diagnoses and lineal regression analysis to determine associations with blood pepsinogen (PGs) levels as measured by serology. The GA genotype of HSP70-2 was associated with increased risk of gastric cancer (OR= 3.42; 95% CI= 1.27-9.21; p= 0.015) and duodenal ulcer (OR= 2.57; 95% CI= 1.03-6.36; p= 0.042) as compared to the GG genotype. Persons with C carrier genotypes of HSP70-Hom were significantly less susceptible to gastric cancer than those with the TT genotype (OR= 0.29; 95% CI= 0.09-0.87; p= 0.027). The C carrier genotype was associated with lower PGI concentrations but none of the polymorphisms were associated with PGI/PGII. Polymorphisms of HSP70 genes are associated with the development of gastric cancer and duodenal ulcers in a population at high risk for gastric cancer in Costa Rica.