MAML2 基因变异对胶质瘤易感性和预后的影响。

Effects of the MAML2 genetic variants in glioma susceptibility and prognosis.

机构信息

Department of Neurosurgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.

Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.

出版信息

Biosci Rep. 2019 Oct 30;39(10). doi: 10.1042/BSR20192091.

DOI:10.1042/BSR20192091

PMID:31652449

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6822528/

Abstract

BACKGROUND

Abnormal expression of the mastermind-like transcriptional co-activator 2 (MAML2) gene is oncogenic in several human cancers, including glioma. However, the relevance of MAML2 variants with glioma remains unknown. We aimed to investigate the role of MAML2 polymorphisms in glioma risk and prognosis among the Chinese Han population.

METHODS

Seven MAML2 single-nucleotide polymorphisms (SNPs) were genotyped using Agena MassARRAY system among 575 patients with glioma and 500 age- and gender-matched healthy controls. Logistic regression was used to estimate the association between MAML2 polymorphisms and glioma risk by calculating odds ratios (ORs) and 95% confidence intervals (CI). Kaplan-Meier survival analysis and univariate, multivariate Cox proportional hazard regression analyses for hazard ratios (HRs) and 95% CIs were performed to evaluate the contribution of MAML2 polymorphisms to glioma prognosis.

RESULTS

MAML2 rs7938889 and rs485842 polymorphisms were associated with the reduced risk of glioma (OR = 0.69, P=0.023; and OR = 0.81, P=0.032, respectively). Rs7115578 polymorphism had a lower susceptibility to glioma in males (OR = 0.68, P=0.034), while rs4598633 variant with a higher risk in females (OR = 1.66, P=0.016). Additionally, rs7115578 AG genotype represented a poorer prognosis of glioma (HR = 1.24, P=0.033) and astrocytoma (log-rank P=0.037, HR = 1.31, P=0.036). Furthermore, rs11021499 polymorphism had lower overall survival (OS) and progression-free survival (PFS) in patients with low-grade glioma.

CONCLUSION

We provided some novel data suggesting MAML2 polymorphisms might contribute to glioma risk and prognosis. Future studies are warranted to validate these findings and characterize mechanisms underlying these associations.

摘要

背景

在包括神经胶质瘤在内的几种人类癌症中，主脑样转录共激活因子 2（MAML2）基因的异常表达是致癌的。然而，MAML2 变体与神经胶质瘤的相关性尚不清楚。我们旨在研究 MAML2 多态性在中国汉族人群中与神经胶质瘤风险和预后的关系。

方法

采用 Agena MassARRAY 系统对 575 例神经胶质瘤患者和 500 例年龄和性别匹配的健康对照者的 7 个 MAML2 单核苷酸多态性（SNP）进行基因分型。采用 logistic 回归计算比值比（OR）及其 95%置信区间（CI），以评估 MAML2 多态性与神经胶质瘤风险之间的关系。采用 Kaplan-Meier 生存分析和单因素、多因素 Cox 比例风险回归分析评估危险比（HR）及其 95%CI，以评估 MAML2 多态性对神经胶质瘤预后的贡献。

结果

MAML2 rs7938889 和 rs485842 多态性与神经胶质瘤风险降低相关（OR=0.69，P=0.023；OR=0.81，P=0.032）。rs7115578 多态性在男性中对神经胶质瘤的易感性较低（OR=0.68，P=0.034），而 rs4598633 变异在女性中具有较高的风险（OR=1.66，P=0.016）。此外，rs7115578 AG 基因型代表神经胶质瘤（HR=1.24，P=0.033）和星形细胞瘤（log-rank P=0.037，HR=1.31，P=0.036）预后不良。此外，rs11021499 多态性与低级别神经胶质瘤患者的总生存（OS）和无进展生存（PFS）较低有关。