HLA polymorphisms are associated with Helicobacter pylori infected gastric cancer in a high risk population, China.

Helicobacter pylori is one of the most common bacterial infections associated with an increased risk of gastric cancer, but its association with host factors, particularly polymorphisms of the immune response genes, such as human leukocyte antigen (HLA) genes, is still unclear. To investigate the role of HLA polymorphisms in the risk of gastric cancer among subjects with H. pylori infection, a case-control study involving 52 gastric cancer patients and 139 non-cancer controls was conducted in Linqu County, China, an area with a high incidence of gastric cancer. Polymorphisms of HLA class I and class II alleles were determined by PCR with sequence-specific primers (PCR-SSP). The information about H. pylori infection was obtained from previous records. Among 48 class I and 19 class II HLA alleles detected in this study, two alleles, CW03 and DRB101, were found to be distributed significantly differently between patients and controls [odds ratio(OR)=1.95, 95% confidence interval (CI)=1.13-3.35, P=0.017 and OR=4.39, 95% CI=1.39-13.84, P=0.012, respectively). The OR of gastric cancer risk in individuals carrying CW03/CW03 or CW03/CWN was 2.06, 95% CI=1.05-4.02, P=0.035, while the OR was 3.49, 95% CI=1.0-12.4, P=0.04 for DRB101/DRB101 or DRB101/DRB1N carriers. The analysis of the interaction between H. pylori infection and HLA risk genotypes of CW03 or DRB101 revealed that the effect of CW03 and DRB101 genotypes on gastric cancer risk was manifested stronger in H. pylori-positive individuals (OR=5.30, 95% CI=1.73-16.29, P=0.004 and OR=13.38, 95% CI=2.52-70.98, P=0.002, respectively) than in H. pylori-negative ones (OR=1.25, 95% CI=0.25-6.12, P=0.785 and OR=2.26, 95% CI=0.18-28.88, P=0.531, respectively). The combined effect of the two risk HLA genotypes on gastric cancer risk was also analysed. The result showed that the individuals carrying both the CW03 and DRB101 alleles could only be found in cancer patients (5/52), and not in controls (0/139), further suggesting that CW03 and DRB101 are risk alleles advancing the progression of tumorigenesis. These observations demonstrate that host HLA genotypes may play an important role in the risk of gastric cancer, especially among persons with H. pylori infection.