Metabolite genome-wide association studies (mGWAS) are key for understanding the genetic regulation of metabolites in complex diseases including cancers. Although mGWAS has revealed hundreds of metabolomics quantitative trait loci (mQTLs) in the general population, data relating to gastric cancer (GC) are still incomplete. We identified mQTLs associated with GC by analyzing genome-wide and metabolome-wide datasets generated from 233 GC patients and 233 healthy controls. Twenty-two metabolites were statistically different between GC cases and healthy controls, and all of them were associated with the risk of gastric cancer. mGWAS analyses further revealed that 9 single nucleotide polymorphisms (SNPs) were significantly associated with 3 metabolites. Of these 9 SNPs, 6 loci were never reported in the previous mGWAS studies. Surprisingly, 4 of 9 SNPs were significantly enriched in genes involved in the T cell receptor signaling pathway. Our study unveiled several novel GC metabolite and genetic biomarkers, which may be implicated in the prevention and diagnosis of gastric cancer.

中文翻译：

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mGWAS 鉴定与胃癌强相关的六个新的单核苷酸多态性位点

代谢物全基因组关联研究 (mGWAS) 是了解包括癌症在内的复杂疾病中代谢物遗传调控的关键。尽管 mGWAS 已经在普通人群中揭示了数百个代谢组学数量性状基因座 (mQTL)，但与胃癌 (GC) 相关的数据仍然不完整。我们通过分析从 233 名 GC 患者和 233 名健康对照产生的全基因组和全代谢组数据集，确定了与 GC 相关的 mQTL。GC 病例与健康对照者之间 22 种代谢物具有统计学差异，且均与胃癌风险相关。mGWAS 分析进一步揭示了 9 个单核苷酸多态性 (SNP) 与 3 个代谢物显着相关。在这 9 个 SNP 中，有 6 个基因座在之前的 mGWAS 研究中从未报道过。出奇，9 个 SNP 中有 4 个显着富含参与 T 细胞受体信号通路的基因。我们的研究揭示了几种新的 GC 代谢物和遗传生物标志物，它们可能与胃癌的预防和诊断有关。