The Glu69Asp Polymorphism of EME1 Gene is Associated with an Increased Risk of Hepatocellular Carcinoma in Guangxi Population, China.
The Glu69Asp Polymorphism of EME1 Gene is Associated with an Increased Risk of Hepatocellular Carcinoma in Guangxi Population, China.
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DOI：
10.2147/ijgm.s383261
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发表时间：
2022
影响因子：
2.3
通讯作者：
中科院分区：
文献类型：
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必需减数分裂核酸内切酶1同源物1（EME 1）的功能障碍可导致基因组不稳定和肿瘤发生。EME 1基因的单核苷酸多态性（SNPs）已被报道与几种癌症的风险相关，但其与肝细胞癌（HCC）的相关性尚未研究。本研究旨在确定EME 1 SNPs与HCC风险之间的关联。该研究包括来自中国南方广西人群的645名HCC患者和649名健康对照，并利用Atria MassARRAY平台对EME 1基因的三个功能性SNP（Glu 69 Asp：rs3760413 A>C，Ile 350 Thr：rs 12450550 T>C和rs 11868055 A>G）进行基因分型。rs3760413 C变异基因型（AC+CC：Glu/Asp+Asp/Asp）与AA（Glu/Glu）基因型相比，其HCC发病风险是AA（Glu/Glu）基因型的1.419倍（校正OR = 1.419，95%CI = 1.017-1.980），等位基因C以剂量依赖方式增加HCC发病风险（Ptrend = 0.017）。此外，rs3760413 C变异基因型的影响在饮用池塘/沟渠水的个体中（校正OR = 3.956，95%CI = 1.413-11.076）比从不饮用的个体更明显（P = 0.033）。我们进一步观察到潜在致癌物微囊藻毒素-LR对rs3760413 C变异基因型携带者外周血单个核细胞DNA氧化损伤的诱导作用显著高于AA基因型携带者（P = 0.006）。将rs3760413 A>C多态性与环境危险因素相结合，构建了预测HCC风险的诺模图，具有良好的区分能力（一致性指数= 0.892，95% CI：0.874-0.911）和良好的校准（平均绝对误差= 0.005）。提示EME 1基因Glu 69 Asp错义多态性（rs3760413）与广西人群肝癌的发病风险相关，可能是广西人群肝癌的易感生物标志物。
The dysfunction of Essential meiotic endonuclease 1 homolog 1 (EME1) can lead to genomic instability and tumorigenesis. Single nucleotide polymorphisms (SNPs) in the EME1 gene have been reported to be associated with the risk of several cancers, but its association with hepatocellular carcinoma (HCC) has not been investigated. This study aimed to determine the association between EME1 SNPs and the risk of HCC. This study included 645 HCC patients and 649 healthy controls from a Guangxi population of Southern China, and genotyped three functional SNPs (Glu69Asp: rs3760413A>C, Ile350Thr: rs12450550T>C, and rs11868055A>G) of the EME1 gene utilizing the Agena MassARRAY platform. The rs3760413C variant genotypes (AC+CC: Glu/Asp+Asp/Asp) conferred a 1.419-fold risk of HCC compared to the AA (Glu/Glu) genotype (adjusted OR = 1.419, 95% CI = 1.017–1.980), and the allele C increased the risk of HCC in a dose-dependent manner (Ptrend = 0.017). Moreover, the effects of the rs3760413C variant genotypes were more pronounced in individuals who drank pond/ditch water (adjusted OR = 3.956, 95% CI = 1.413–11.076) than in those who never drank (P = 0.033). We further observed that a potential carcinogen microcystin-LR induced more DNA oxidative damages in peripheral blood mononuclear cells from the carriers of rs3760413C variant genotypes than those from the subjects with AA genotype (P = 0.006). A nomogram was also constructed combining the rs3760413A>C polymorphism and environmental risk factors for predicting HCC risk with a good discriminatory ability (concordance index = 0.892, 95% CI: 0.874–0.911) and good calibration (mean absolute error = 0.005). Our data suggest that the Glu69Asp missense polymorphism (rs3760413) of EME1 gene is associated with the risk of HCC, which may be a susceptible biomarker of HCC in the Guangxi population.