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TP53 和 RPA3 基因突变与中国汉族人群罹患脑胶质瘤的风险相关。

TP53 and RPA3 gene variations were associated with risk of glioma in a Chinese Han population.

机构信息

National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, People's Republic of China.

出版信息

Cancer Biother Radiopharm. 2013 Apr;28(3):248-53. doi: 10.1089/cbr.2012.1291.

Abstract

Recent advances in human genetic studies have opened new avenues for the identification of susceptibility genes for many complex genetic disorders, especially in the field of rare cancers such as glioma. Glioma is one of the least understood human tumors and the etiology for glioma is barely known. Hundreds of single-nucleotide polymorphisms (SNPs) are found to be related to the risk of glioma in previous studies. This study is committed to investigate the role of heredity in this disorder. To examine and validate how common variants contribute to glioma susceptibility in the Han Chinese population, we evaluated 12 tagging SNPs in a case-control study in the Chinese Han population from Xi'an city of China (301 cases and 302 controls). Overall, two protective alleles and one risk allele for glioma were found by genetic model analyses. In dominant model, the allele "T" of rs6947203 in the RPA3 gene acts as a protective allele [odds ratio (OR), 0.59; 95% confidence interval (CI), 0.22-0.90; p=0.014]. In recessive model, the allele "C" of rs1042522 in the TP53 gene acts as a risk allele (OR, 1.65; 95% CI, 1.05-2.59; p=0.0314). In additive model, the allele "G" of rs4140805 in the RPA3 gene (OR, 0.73; 95% CI, 0.53-0.99; p=0.0437) and the allele "T" of rs6947203 in the RPA3 gene (OR, 0.62; 95% CI, 0.42-0.92; p=0.0177) both act as protective alleles. We also observed a haplotype of "CC" in the TP53 gene with an increased risk of 34% of developing glioma (p=0.0306). Our results, combined with previous studies, ascertain the potential role of the TP53 gene to glioma onset.

摘要

最近在人类遗传学研究方面的进展为许多复杂遗传疾病的易感基因的鉴定开辟了新的途径,尤其是在胶质瘤等罕见癌症领域。胶质瘤是人类肿瘤中了解最少的一种,其病因几乎未知。以前的研究发现,成百上千个单核苷酸多态性(SNP)与胶质瘤的发病风险有关。本研究致力于探讨遗传在这种疾病中的作用。为了研究常见变异如何在中国汉族人群中导致胶质瘤易感性,我们在中国西安汉族人群中进行了一项病例对照研究,评估了 12 个标记 SNP(301 例病例和 302 例对照)。总体而言,通过遗传模型分析发现了两个保护等位基因和一个风险等位基因。在显性模型中,RPA3 基因 rs6947203 的等位基因“T”作为保护等位基因发挥作用[比值比(OR),0.59;95%置信区间(CI),0.22-0.90;p=0.014]。在隐性模型中,TP53 基因 rs1042522 的等位基因“C”作为风险等位基因发挥作用(OR,1.65;95%CI,1.05-2.59;p=0.0314)。在加性模型中,RPA3 基因 rs4140805 的等位基因“G”(OR,0.73;95%CI,0.53-0.99;p=0.0437)和 RPA3 基因 rs6947203 的等位基因“T”(OR,0.62;95%CI,0.42-0.92;p=0.0177)均作为保护等位基因发挥作用。我们还观察到 TP53 基因的“CC”单倍型与胶质瘤发病风险增加 34%有关(p=0.0306)。我们的结果与以前的研究相结合,证实了 TP53 基因在胶质瘤发病中的潜在作用。

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