Distinct human leukocyte antigen (HLA)-DQ genes have been associated with an increased or reduced risk for gastric cancer, but its association with Helicobacter pylori status is controversial. In the present study we evaluated the influence of host HLA DQA1 and DQB1 loci, H. pylori genotype, and socio-economic factors on predicting H. pylori-associated distal gastric cancer in a southern European population.
In a prospective case-control (1 : 2) study, 42 patients with H. pylori-associated distal gastric cancer were matched by age (+/-5 years) and gender to 84 patients with H. pylori-associated benign gastroduodenal disease (controls). The level of education received, smoking status, alcohol consumption, origin and familial history of gastric cancer were registered at inclusion. HLA DQA1 and DQB1 typing and H. pylori genotyping were determined from endoscopic gastric mucosal biopsies.
Compared with control patients, a positive association with cagA(+) strains (p < .002) and a negative association with vacA-s2 strains (p < .02) was found in patients with distal gastric cancer. At the DQB1 locus, the (*)0602 allele was more frequent in distal gastric cancer than in controls (26.2% vs. 4.8%; p < .005). After correction for multiple comparisons (exact multiple regression analysis) the cagA(+) status and the DQB1(*)0602 allele were associated with an increased distal gastric cancer risk (OR 3.7; 95% CI = 1.33-12.26 and OR 4.82; 95% CI = 1.24-19.83, respectively) whereas the vacA-s2 status was associated with a decreased risk (OR 0.33; 95% CI = 0.10-0.94).
Our findings suggest that in the H. pylori-infected southern European population, the cagA genotype and the HLA-DQB1(*)0602 gene confer an increased risk for distal gastric cancer.