NOD1 and NOD2 genetic variants in association with risk of gastric cancer and its precursors in a Chinese population

Abstract

Background: Genetic variants of nucleotide-binding oligomerization domain-containing protein (NOD) may influence the outcome of Helicobacter pylori (H. pylori) infection and gastric carcinogenesis. To explore genetic variants of NOD1 and NOD2 in association with gastric cancer (GC) and its precursors, a population-based study was conducted in Linqu County, China. Methods: TagSNPs of NOD1 and NOD2 were genotyped by Sequenom MASS array in 132 GCs, and 1,198 subjects with precancerous gastric lesions, and were correlated with evolution of gastric lesions in 766 subjects with follow-up data. Results: Among seven tagSNPs, NOD1 rs2709800 and NOD2 rs718226 were associated with gastric lesions. NOD1 rs2709800 TG genotype carriers had a decreased risk of intestinal metaplasia (IM, OR: 0.53; 95%CI: 0.31-0.92), while NOD2 rs718226 G allele (AG/GG) showed increased risks of dysplasia (DYS, OR: 2.96; 95%CI: 1.86-4.71) and GC (OR: 2.35; 95% CI: 1.24-4.46). Moreover, an additive interaction between rs718226 and H. pylori was found in DYS or GC with synergy index of 3.08 (95%CI: 1.38-6.87) or 3.99 (95%CI: 1.55-10.22), respectively. The follow-up data indicated that NOD2 rs2111235 C allele (OR: 0.52; 95% CI: 0.32-0.83) and rs7205423 G allele (OR: 0.56; 95%CI: 0.35-0.89) were associated with decreased risk of progression in H. pylori-infected subjects. Conclusions: NOD1 rs2709800, NOD2 rs718226, rs2111235, rs7205423 and interaction between rs718226 and H. pylori infection may be related to risk of gastric lesions.