Survival prediction in patients with glioblastoma multiforme by human telomerase genetic variation

被引:64
作者
Wang, L
Wei, QY
Wang, LE
Aldape, KD
Cao, YM
Okcu, MF
Hess, KR
El-Zein, R
Gilbert, MR
Woo, SY
Prabhu, SS
Fuller, GN
Bondy, ML
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Unit 1340, Houston, TX 77230 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77230 USA
[3] Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77230 USA
[4] Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77230 USA
[5] Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77230 USA
[6] Univ Texas, MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77230 USA
[7] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA
关键词
D O I
10.1200/JCO.2005.04.0402
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Glioblastoma multiforme (GBM) is the most common and aggressive glioma with the poorest survival. Use of biomarkers for screening patients with GBM may be used to modify treatments and improve outcomes. The level of human telomerase (hTERT) expression is an independent predictor of outcome of many cancers, and a functional variant of hTERT MNS16A (shorter tandem repeats or short [S] allele) is associated with increased hTERT expression. We investigated whether hTERT MNS16A variant genotype predicted survival in GBM patients. Patients and Methods We genotyped hTERT MNS16A in 299 1 patients using polymerase chain reaction and determined hTERTgenotype by classifying the DNA band of 243 or 272 base pairs (bp) as S allele and 302 or 333 bp as long (L) allele. We compared overall survival using Kaplan-Meier estimates and equality of survival distributions using the log-rank test, and we computed univariate and multivariate Cox proportional hazards models to estimate the effects of selected variables. Results Overall survival differed significantly by hTERT MNS16A genotype, with median survivals of 25.1, 14.7, and 14.6 months for the SS, SL, and ILL genotypes, respectively. Compared with the SS genotype, the hazard ratios for the SL and LL genotypes were 1.69 and 1.87, respectively, after adjustment for other factors. Multivariate Cox regression analysis showed an independent statistically significant association between the hTERT MNS16A variant genotype and outcome. Conclusion A functional hTERT MNS16A genotype is a potential biomarker for assessment of survival outcome of GBM. Larger studies are needed to verify these findings.
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页码:1627 / 1632
页数:6
相关论文
共 47 条
[1]   Polymorphisms within glutathione S-transferase genes and initial response to glucocorticoids in childhood acute lymphoblastic leukaemia [J].
Anderer, G ;
Schrappe, M ;
Brechlin, AM ;
Lauten, M ;
Muti, P ;
Welte, K ;
Stanulla, M .
PHARMACOGENETICS, 2000, 10 (08) :715-726
[2]  
[Anonymous], 2004, STAT REP PRIM BRAIN
[3]   Loss of chromosome 10 is an independent prognostic factor in high-grade gliomas [J].
Balesaria, S ;
Brock, C ;
Bower, M ;
Clark, J ;
Nicholson, SK ;
Lewis, P ;
de Sanctis, S ;
Evans, H ;
Peterson, D ;
Mendoza, N ;
Glaser, MG ;
Newlands, ES ;
Fisher, RA .
BRITISH JOURNAL OF CANCER, 1999, 81 (08) :1371-1377
[4]  
Brada M, 2000, SEMIN ONCOL, V27, pS11
[5]   Mapping of the gene for the human telomerase reverse transcriptase, hTERT, to chromosome 5p15.33 by fluorescence in situ hybridization [J].
Bryce, LA ;
Morrison, N ;
Hoare, SF ;
Muir, S ;
Keith, WN .
NEOPLASIA, 2000, 2 (03) :197-201
[6]   Novel anticancer drug discovery [J].
Buolamwini, JK .
CURRENT OPINION IN CHEMICAL BIOLOGY, 1999, 3 (04) :500-509
[7]   Years of life lost (YLL) from cancer is an important measure of population burden - and should be considered when allocating research funds [J].
Burnet, NG ;
Jefferies, SJ ;
Benson, RJ ;
Hunt, DP ;
Treasure, FP .
BRITISH JOURNAL OF CANCER, 2005, 92 (02) :241-245
[8]   Telomerase activity and survival of patients with node-positive breast cancer [J].
Clark, GM ;
Osborne, CK ;
Levitt, D ;
Wu, F ;
Kim, NW .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1997, 89 (24) :1874-1881
[9]  
COLLETT D, 2000, MODELING SURVIVAL DA, P111
[10]   Human telomerase and its regulation [J].
Cong, YS ;
Wright, WE ;
Shay, JW .
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 2002, 66 (03) :407-+