Wrensch Margaret, Wiencke John K, Wiemels Joe, Miike Rei, Patoka Joe, Moghadassi Michelle, McMillan Alex, Kelsey Karl T, Aldape Kenneth, Lamborn Kathleen R, Parsa Andrew T, Sison Jennette D, Prados Michael D
Department of Neurological Surgery, University of California San Francisco, San Francisco, California 94102, USA.
Cancer Res. 2006 Apr 15;66(8):4531-41. doi: 10.1158/0008-5472.CAN-05-4032.
In population-based glioma patients, we examined survival in relation to potentially pertinent constitutive polymorphisms, serologic factors, and tumor genetic and protein alterations in epidermal growth factor receptor (EGFR), MDM2, and TP53. Subjects were newly diagnosed adults residing in the San Francisco Bay Surveillance Epidemiology and End Results Area during 1991 to 1994 and 1997 to 1999 with central neuropathology review (n = 873). Subjects provided blood for serologic studies of IgE and IgG to four herpes viruses and constitutive specimens for genotyping 22 polymorphisms in 13 genes (n = 471). We obtained 595 of 697 astrocytic tumors for marker studies. We determined treatments, vital status, and other factors using registry, interview, medical record, and active follow-up data. Cox regressions for survival were adjusted for age, gender, ethnicity, study series, resection versus biopsy only, radiation, and chemotherapy. Using a stringent P < 0.001, glioma survival was associated with ERCC1 C8092A [hazard ratio (HR), 0.72; 95% confidence limits (95% CL), 0.60-0.86; P = 0.0004] and GSTT1 deletion (HR, 1.64; 95% CL, 1.25-2.16; P = 0.0004); glioblastoma patients with elevated IgE had 9 months longer survival than those with normal or borderline IgE levels (HR, 0.62; 95% CL, 0.47-0.82; P = 0.0007), and EGFR expression in anaplastic astrocytoma was associated with nearly 3-fold poorer survival (HR, 2.97; 95% CL, 1.70-5.19; P = 0.0001). Based on our and others' findings, we recommend further studies to (a) understand relationships of elevated IgE levels and other immunologic factors with improved glioblastoma survival potentially relevant to immunologic therapies and (b) determine which inherited ERCC1 variants or other variants in the 19q13.3 region influence survival. We also suggest that tumor EGFR expression be incorporated into clinical evaluation of anaplastic astrocytoma patients.
在基于人群的胶质瘤患者中，我们研究了与潜在相关的组成型多态性、血清学因素以及表皮生长因子受体（EGFR）、MDM2和TP53的肿瘤基因及蛋白质改变相关的生存率。研究对象为1991年至1994年以及1997年至1999年期间居住在旧金山湾区监测流行病学和最终结果区域的新诊断成年患者，均经过中枢神经病理学复查（n = 873）。研究对象提供血液用于对四种疱疹病毒进行IgE和IgG的血清学研究，并提供组成型标本用于对13个基因中的22种多态性进行基因分型（n = 471）。我们从697例星形细胞瘤中获取了595例用于标志物研究。我们通过登记、访谈、病历及主动随访数据确定治疗方法、生命状态及其他因素。生存的Cox回归分析针对年龄、性别、种族、研究系列、仅手术切除与活检、放疗及化疗进行了校正。采用严格的P < 0.001标准，胶质瘤生存率与ERCC1 C8092A [风险比（HR），0.72；95%置信区间（95% CL），0.60 - 0.86；P = 0.0004]和GSTT1缺失（HR，1.64；95% CL，1.25 - 2.16；P = 0.0004）相关；IgE升高的胶质母细胞瘤患者比IgE水平正常或临界的患者生存期长9个月（HR，0.62；95% CL，0.47 - 0.82；P = 0.0007），间变性星形细胞瘤中的EGFR表达与生存期缩短近3倍相关（HR，2.97；95% CL，1.70 - 5.19；P = 0.0001）。基于我们及其他人的研究结果，我们建议进一步开展研究以（a）了解IgE水平升高及其他免疫因素与胶质母细胞瘤生存期改善之间的关系，这可能与免疫治疗相关；（b）确定19q13.3区域中哪些遗传性ERCC变体或其他变体影响生存期。我们还建议将肿瘤EGFR表达纳入间变性星形细胞瘤患者的临床评估中。
