PDF(Pubmed)
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.
摘要：
核心1合酶糖蛋白-N-乙酰半乳糖胺3-β-半乳糖基转移酶1（C1GALT1）已知在胃癌的发展中起关键作用，但很少有研究阐明C1GALT1基因变异与胃癌易感性之间的关联。通过使用来自基因型和表型（dbGAP）数据库的全基因组关联研究数据，我们用逻辑回归模型评估了这些关联，并确定C1GALT1中的rs35999583与胃癌风险相关（奇数比，0.83；95%置信区间[CI]，0.75-0.92；P=3.95×10-4]。C1GALT1mRNA在胃肿瘤组织中表达显著增高，C1GALT1mRNA水平较高的胃癌患者的总生存率较差(风险比，1.33；95%CI，1.05-1.68；Plog-rank=1.90×10-2)。此外，我们发现C1GALT1拷贝数变异在各种免疫细胞中存在差异,C1GALT1mRNA表达与CD4+T细胞和巨噬细胞的浸润水平呈正相关.这些结果强调了C1GALT1的遗传变异可能在胃癌风险中起重要作用，并为C1GALT1成为胃癌易感性和免疫状态的有希望的预测因子提供了新的见解。
