Heat-shock protein (HSP) 70 plays essential roles in cellular response to a variety of environmental stresses or unfavorable conditions. A to G transition at the 1267 position of the HSP70-2 gene confers different levels of HSP70 mRNA expression. We aimed to clarify the effect of HSP70-2 polymorphism on the risk of premalignant condition, on the degree of acute or chronic inflammation in the stomach. A total of 378 individuals participated in this study. Restriction fragment length polymorphism analysis was performed for polymorphisms at 1267 of HSP70-2 gene. Prevalence of intestinal metaplasia was investigated histologically and the degree of histological gastritis in the antrum was classified according to the updated Sydney System. Although a direct association was not observed between HSP70-2 polymorphism and prevalence of intestinal metaplasia, a significant association was found between the BB genotype and lower metaplasia score in individuals who were Helicobacter pylori (H. pylori) positive and aged 60 years or older (BB vs. A carriers; 0.84+/-0.95 vs. 1.23+/-1.01, p=0.0197). When individuals were divided into 3 groups according to the severity of gastric mucosal atrophy: non-atrophic gastritis (NA) group (atrophy score=0 and metaplasia score=0), severe atrophic gastritis (SA) group (atrophy score > or =2 or metaplasia score > or =2), and mild atrophic gastritis (MA) group (all others), the BB genotype was associated with a lower risk of severe atrophy in the SA sub-group (adjusted odds ratio=0.37, 95% confidence interval =0.16-0.84, p=0.0172). The BB genotype of HSP70-2 gene is associated with a reduced risk of gastric pre-malignant condition in H. pylori-infected older individuals.