Association of HLA‐DQB1★0301 and HLA‐DQB1★0602 with Different Subtypes of Gastric Cancer in Taiwan

Gastric cancer (GC) is a heterogeneous disorder with multifactorial etiologies. Genetic predisposition, environmental factors, and Helicobacter pylori infection are thought to interact in the manifestation of GC. Particular human leukocyte antigen (HLA) alleles play a pivotal role in cellular immunity and may be an important genetically determined host trait. To elucidate the association between the genotype of HLA class II genes and the clinical phenotype of GC, polymorphisms of HLA‐DRB1 and HLA‐DQB1 were determined by polymerase chain reaction with sequence‐specific primers in 106 Taiwanese patients with GC and in 208 healthy controls. Comparison of allele frequencies between GC patients and healthy controls showed no significant difference at the HLA‐DRB1 locus. Patients with GC had a higher frequency of DQB1★0602 (9.4% vs. 3.6%, P<0.05, odds ratio 2.79, 95% confidence interval 1.41–5.47) and a lower frequency of DQB1★0301 (14.6% vs. 23.8%, P<0.05, odds ratio 0.55, 95% confidence interval 0.35–0.85) compared to healthy controls. Correlation of HLA‐DQB1 status with clinicopathologic features revealed predominance of male gender (16/3 vs. 50/37, P<0.05) and proximal location (12/7 vs. 28/59, P<0.05) in patients with positive HLA‐DBQ1★0602 compared to those with negative HLA‐DBQ1★0602. In contrast, a higher ratio of diffuse/intestinal subtype (20/10 vs. 30/46, P<0.05) and a lower seropositivity of Helicobacter pylori (14/30 vs. 58/76, P<0.005) were noted in patients with positive HLA‐DQB1★0301 compared to those with negative HLA‐DQB1★0301. In conclusion, HLA‐DQB1★0602 confers susceptibility to gastric cancer, especially for male Taiwanese and proximal tumor location, while HLA‐DQB1★0301 may have a protective effect on GC, probably through resistance to Helicobacter pyloriinfection. HLA‐DQB1 alleles are associated with susceptibility or resistance to GC and also influence its clinical features.