Genetic variants in C1GALT1 are associated with gastric cancer risk and immune infiltrations

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1 (C1GALT1) is known to play a critical role in the development of gastric cancer, but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer susceptibility. By using the GWAS data from the database of Genotype and Phenotype (dbGAP), we evaluated these associations with a logistic regression model and identified that the rs35999583 in C1GALT1 was associated with gastric cancer risk odd ratio = 0.83, 95% confidence interval = 0.75–0.92, P = 3.95 × 10⁻⁴. C1GALT1 mRNA expression was significantly higher in gastric tumor tissues, and gastric cancer patients with high C1GALT1 mRNA levels had the worse overall survival rates hazards ratio = 1.33 (1.05–1.68), P_log–rank = 1.90 × 10⁻². Furthermore, we found that C1GALT1 copy number variations differed in various immune cells and C1GALT1 mRNA expression was positively correlated with the infiltrating levels of CD4⁺ T cells and macrophages. These results highlight that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 to be a promising predictor of gastric cancer susceptibility and immune status.