Genetic Variation in A4GNT in Relation to Helicobacter pylori Serology and Gastric Cancer Risk

Background: Helicobacter pylori, a known risk factor of gastric cancer, rarely colonize the deeper portion of normal gastric glands, where the mucus is rich in α-1,4-linked N-acetylglucosamine capped O-glycans, that strongly inhibit H. pylori growth in vitro. Materials and methods:  We investigated the association between genetic variation in the O-glycan transferase encoding gene (a4GnT) and H. pylori infection and gastric cancer risk using a Polish population-based case–control study (273 gastric cancer patients and 377 controls). Results:  A haplotype at the rs2622694–rs397266 locus was associated with H. pylori infection, with the A-A haplotype associated with a higher risk compared with the most frequent G-G haplotype (odds ratio 2.30; 95% confidence interval 1.35–3.92). The association remained significant after correction for multiple tests (global p value: nominal 0.002, empirical 0.045). Neither this haplotype nor the tagSNPs were associated with overall gastric cancer risk. Conclusion: a4GnT genetic variation may be relevant to H. pylori infection, but not to gastric cancer risk.