Polymorphisms in HLA-DQ genes, together with age, sex, and Helicobacter pylori infection, as potential biomarkers for the early diagnosis of gastric cancer.

Abstract

Polymorphisms in inflammation-related genes are factors associated with the development of gastroduodenal diseases in Helicobacter pylori-infected individuals. We aimed to analyze polymorphisms in HLA-DQ, together with other host and H.pylori variables as risk factors for precancerous and cancerous gastric lesions. 1052 individuals were studied, including nonatrophic gastritis (NAG), intestinal metaplasia (IM), gastric cancer (GC) or duodenal ulcer (DU) patients, and healthy volunteers. Patients with alleles DQA*01:01 (OR 0.78), *01:02 (OR 0.29), *01:03 (OR 0.31), and DQB*02:01/02 (OR 0.40) showed a reduced risk for GC. A multivariate logistic regression analyses showed that patients with homozygote genotypes DQA1*03:01 (OR 7.27) and DQA1*04:01 (OR 8.99) and DQB1*05:01:01 (OR 12.04) were at significantly increased risk for GC. Multivariate analyses also demonstrated that age (OR>10.0) and gender (OR>2.0) were variables that influenced significantly the risk for GC, while H.pylori infection (OR>2.5) increased the risk for IM. We identified HLA-DQ alleles associated with IM and GC, and confirm that age, sex, and H.pylori infection are variables that also influence the risk for disease. The use of multiple markers, HLA-DQ alleles, age, sex, and H.pylori infection may be useful biomarkers for the early diagnosis of patients with IM and GC.