OBJECTIVE:Gastric carcinogenesis is a multi-step process and is influenced by several etiological agents, including the host's genetic factors. Since whether a patient remains with chronic superficial gastritis (CSG) or progresses to either chronic atrophic gastritis (CAG) or gastric carcinoma (GC) could be a genetic predisposition unique in each population, we hypothesized that host human leukocyte antigen (HLA) alleles could be discriminative in predicting the risk of CSG progression to precancerous CAG and GC in Koreans. METHODS:A total of 165 patients with gastric disorders (CSG, 62; CAG, 69 and GC, 34), were selected to investigate the association of HLA class II alleles with the progression of CSG to CAG or GC. HLA genotypes were obtained by the polymerase chain reaction-sequence based typing method. RESULTS:The phenotypic frequencies of DRB1*1101 and DQA1*0505 were significantly higher in the CAG group compared to those in the CSG group. In the subjects with Helicobacter pylori (H. pypori) (+), the frequencies of DRB1*1501 and DQB1*0602 were significantly lower in the CAG compared to those in the CSG. Further analysis showed that sex (P < 0.05, OR = 0.41-0.42) and age (P < 0.05, OR = 1.05) also affected the risk of progression from CSG to CAG in H. pylori (+) patients carrying the DRB1*1501 or DQB1*0602 allele. Additionally, the frequency of DRB1*0404 in the GC group was significantly higher than that in the gastritis group. CONCLUSION:Our findings strongly imply an association between HLA class II alleles and the risk of CAG development and GC progression in Koreans.