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两个新的 STK38L 和 RAB27A 基因遗传变异与胶质瘤易感性相关。

Two novel genetic variants in the STK38L and RAB27A genes are associated with glioma susceptibility.

机构信息

State Key Laboratory of Genetic Engineering, Zhongshan Hospital, Fudan University, and School of Life Sciences, Fudan University, Shanghai, China.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

Int J Cancer. 2019 Nov 1;145(9):2372-2382. doi: 10.1002/ijc.32179. Epub 2019 Mar 18.

Abstract

Glioma is the most common malignant primary brain tumors with poor prognosis. Genome wide association studies (GWAS) of glioma in populations with Western European ancestry were completed in the US and UK. However, our previous results strongly suggest the genetic heterogeneity could be important in glioma risk. To systematically investigate glioma risk-associated variants in Chinese population, we performed a multistage GWAS of glioma in the Han Chinese population, with a total of 3,097 glioma cases and 4,362 controls. In addition to confirming two associations reported in other ancestry groups, this study identified one new risk-associated locus for glioma on chromosome 12p11.23 (rs10842893, p = 2.33x10-12, STK38L) as well as a promising association at 15q15-21.1 (rs4774756, p = 6.12x10-8, RAB27A) in 3,097 glioma cases and 4,362 controls. Our findings demonstrate two novel association between the glioma risk region marked by variant rs10842893 and rs4774756) and glioma risk. These findings may advance the understanding of genetic susceptibility to glioma.

摘要

神经胶质瘤是最常见的恶性原发性脑肿瘤,预后不良。在具有西欧血统的人群中,对神经胶质瘤的全基因组关联研究(GWAS)已经完成,这些研究分别在美国和英国进行。然而,我们之前的研究结果强烈表明遗传异质性可能是神经胶质瘤风险的重要因素。为了系统地研究中国人群中与神经胶质瘤风险相关的变异,我们对汉族人群进行了多阶段的神经胶质瘤 GWAS 研究,共有 3097 例神经胶质瘤病例和 4362 例对照。除了证实了其他血统群体中报告的两个关联之外,这项研究还在染色体 12p11.23 上确定了一个新的与神经胶质瘤相关的风险位点(rs10842893,p = 2.33x10-12,STK38L),以及在 15q15-21.1 上一个有前途的关联位点(rs4774756,p = 6.12x10-8,RAB27A),这些关联在 3097 例神经胶质瘤病例和 4362 例对照中均得到验证。我们的研究结果表明,变异 rs10842893 和 rs4774756 标记的神经胶质瘤风险区域与神经胶质瘤风险之间存在两个新的关联。这些发现可能有助于深入了解神经胶质瘤的遗传易感性。

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