MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and to glioblastoma outcome
MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and to glioblastoma outcome
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DOI：
10.1002/ijc.24363
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发表时间：
2009-08-15
影响因子：
6.4
通讯作者：
Malmer, Beatrice
中科院分区：
文献类型：
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作者：
Andersson, Ulrika;Osterman, Pia;Malmer, Beatrice
人端粒酶逆转录酶（hTERT）基因在大多数恶性肿瘤中上调。已报道可变串联重复序列MNS 16 A对hTERT表达具有功能意义。已发表的关于MNS 16 A变体在脑肿瘤中的临床相关性的数据是矛盾的。目前在北欧国家和英国进行的以人群为基础的研究评估了648例胶质瘤病例、473例脑膜瘤病例和1,359例年龄、性别和地理位置匹配的对照组中与MNS 16 A小卫星变异相关的脑肿瘤风险和生存率。通过基于PCR的基因分型，将具有240或271个片段的受试者判定为具有短（S）等位基因，将具有299或331个片段的受试者判定为具有长（L）等位基因。神经胶质瘤或脑膜瘤的相对危险度用logistic回归估计，校正年龄、性别和国家。使用Kaplan-Meier估计值分析总生存期，使用对数秩检验和考克斯比例风险比分析生存分布的等同性。MNS 16 A基因型与胶质瘤、胶质母细胞瘤（GBM）和脑膜瘤的发生风险无关。对于GBM，LL、LS和SS基因型的中位生存期分别为15.3、11.0和10.7个月; LS基因型与LL相比的风险比显著增加HR 2.44（1.56-3.82），SS基因型与LL相比的风险比无显著增加HR 1.46（0.81-2.61）。当比较LL与具有潜在功能变体LS和SS之一时，HR为2.10（1.41-3.1）。然而，不支持功能性，因为HR没有随S等位基因数量增加的趋势。从我们和以前的研究中收集的关于MNS 16 A基因型的风险和生存率的数据是矛盾的，需要进一步的研究。(C)2009年UICC
The human telomerase reverse transcriptase (hTERT) gene is upregulated in a majority of malignant tumours. A variable tandem repeat, MNS16A, has been reported to be of functional significance for hTERT expression. Published data on the clinical relevance of MNS16A variants in brain tumours have been contradictory. The present population-based study in the Nordic countries and the United Kingdom evaluated brain-tumour risk and survival in relation to MNS16A minisatellite variants in 648 glioma cases, 473 meningioma cases and 1,359 age, sex and geographically matched controls. By PCR-based genotyping all study, subjects with fragments of 240 or 271 by were,judged as having short (S) alleles and subjects with 299 or 331 by fragments as having long (L) alleles. Relative risk of glioma or meningioma was estimated with logistic regression adjusting for age, sex and country. Overall survival,vas analysed using Kaplan-Meier estimates and equality of survival distributions using the log-rank test and Cox proportional hazard ratios. The MNS16A genotype,vas not associated with risk of occurrence of glioma, glioblastoma (GBM) or meningioma. For GBM there were median survivals of 15.3, 11.0 and 10.7 months for the LL, LS and SS genotypes, respectively; the hazard ratio for having the LS genotype compared with the LL was significantly increased HR 2.44 (1.56-3.82) and having the SS genotype versus the LL was nonsignificanlty increased HR 1.46 (0.81-2.61). When comparing the LL versus having one of the potentially functional variants LS and SS, the HR,vas 2.10 (1.41-3.1). However, functionality was not supported as there was no trend towards increasing HR with number of S alleles. Collected data from our and previous studies regarding both risk and survival for the MNS16A genotypes are contradictory and warrant further investigations. (C) 2009 UICC