Genetic variants in C1GALT1 are associated with gastric cancer risk by influencing immune infiltration

Abstract

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 risk. By using the genome-wide association study data from the database of Genotype and Phenotype (dbGAP), we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk (odds ratio, 0.83; 95% confidence interval [CI], 0.75-0.92; P = 3.95 × 10⁻⁴). C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues, and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates (hazards ratio, 1.33; 95% CI, 1.05-1.68; P_log-rank = 1.90 × 10⁻²). Furthermore, we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4⁺ T cells and macrophages. These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.

Keywords

O-glycosylation / genetic variants / immune status / gastric cancer

Fundings

The present study was funded by the National Key R&D Program of China (Grant Nos. 2018YFC1313100 and 2018YFC1313102), the National Natural Science Foundation of China (Grant No. 81773539), Collaborative Innovation Center for Cancer Personalized Medicine, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

Acknowledgments

The authors would like to thank Dr. Xudong Song of the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University for providing assistance with sample collection.

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