Munch Tina Noergaard, Gørtz Sanne, Wohlfahrt Jan, Melbye Mads
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (T.N.M., S.G., J.W., M.M.); Department of Neurosurgery, Copenhagen University Hospital, Denmark (T.N.M.).
Neuro Oncol. 2015 May;17(5):718-24. doi: 10.1093/neuonc/nou312. Epub 2014 Nov 21.
Neoplastic transformation of damaged astrocytes has been proposed as a possible pathological mechanism behind malignant astrocytic tumors. This study investigated the association between structural brain injuries causing reactive astrogliosis and long-term risk for malignant astrocytic tumors.
The cohort consisted of all individuals living in Denmark between 1978 and 2011. The personal identification number assigned to all individuals allowed retrieval of diagnoses of traumatic brain injury, cerebral ischemic infarction, and intracerebral hemorrhage from the National Patient Discharge Register. Diagnoses of anaplastic astrocytoma and glioblastoma multiforme (World Health Organization grades III and IV) were retrieved from the Danish Cancer Registry. Rate ratios (RR's) were estimated using log-linear Poisson regression.
In a cohort of 8.2 million individuals, 404 812 experienced a structural brain injury and 6152 developed a malignant astrocytic tumor. No significant association was observed 1-4 years after a structural brain injury (RR = 1.14; 95% CI: 0.87-1.46), whereas the long-term (5+ y) risk for malignant astrocytic tumors was significantly reduced (RR = 0.68; 95% CI: 0.49-0.90) compared with no injury. The specific long-term risks by type of injury were: traumatic brain injury RR = 0.32 (95% CI: 0.10-0.75); cerebral ischemic infarction RR = 0.69 (95% CI: 0.47-0.96); and intracerebral hemorrhage RR = 1.39 (95% CI: 0.64-2.60).
We found no evidence for an association between structural brain injury and malignant astrocytic tumors within the first 5 years of follow-up. However, our study indicated a protective effect of astrogliosis-causing injuries 5 or more years after structural brain injury.
受损星形胶质细胞的肿瘤性转化被认为是恶性星形细胞瘤潜在的病理机制。本研究调查了导致反应性星形胶质细胞增生的结构性脑损伤与恶性星形细胞瘤长期风险之间的关联。
队列研究对象为1978年至2011年间居住在丹麦的所有个体。通过个人身份证号码,从国家患者出院登记处获取创伤性脑损伤、脑缺血性梗死和脑出血的诊断信息。间变性星形细胞瘤和多形性胶质母细胞瘤(世界卫生组织III级和IV级)的诊断信息则从丹麦癌症登记处获取。采用对数线性泊松回归估计率比(RR)。
在820万个体的队列中,404812人经历了结构性脑损伤,6152人发生了恶性星形细胞瘤。结构性脑损伤后1至4年未观察到显著关联(RR = 1.14;95%置信区间:0.87 - 1.46),而与未受伤相比,恶性星形细胞瘤的长期(5年以上)风险显著降低(RR = 0.68;95%置信区间:0.49 - 0.90)。不同类型损伤的具体长期风险为:创伤性脑损伤RR = 0.32(95%置信区间:0.10 - 0.75);脑缺血性梗死RR = 0.69(95%置信区间:0.47 - 0.96);脑出血RR = 1.39(95%置信区间:0.64 - 2.60)。
我们发现在随访的前5年内,没有证据表明结构性脑损伤与恶性星形细胞瘤之间存在关联。然而,我们的研究表明,结构性脑损伤5年或更长时间后,导致星形胶质细胞增生的损伤具有保护作用。