Traumatic glioblastoma: commentary and suggested mechanism

Ohana, Nissim; Benharroch, Daniel; Sheinis, Dimitri; Cohen, Abraham

doi:10.1177/0300060518771265

Cited by 6 publications

(8 citation statements)

References 22 publications

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“…In 1978, Morantz and Shain examined a rat model for neural tumors and found that animals exposed to a cerebral stab wound were more likely to develop gliomas compared with uninjured control animals. Subsequently, a variety of potential mechanisms have been proposed, including alterations in metabolism, inflammation, astrocyte proliferation, and stem cell migration and differentiation . More recently, Richards and colleagues performed single-cell RNA sequencing on glioblastoma stem cells from 26 individuals.…”

Section: Discussionmentioning

confidence: 99%

Traumatic Brain Injury and Subsequent Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars

Stewart,

Howard,

Poltavskiy

et al. 2024

JAMA Netw Open

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ImportanceWhile brain cancer is rare, it has a very poor prognosis and few established risk factors. To date, epidemiologic work examining the potential association of traumatic brain injury (TBI) with the subsequent risk of brain cancer is conflicting. Further data may be useful.ObjectiveTo examine whether a history of TBI exposure is associated with the subsequent development of brain cancer.Design, Setting, and ParticipantsA retrospective cohort study was conducted from October 1, 2004, to September 20, 2019, and data analysis was performed between January 1 and June 26, 2023. The median follow-up for the cohort was 7.2 (IQR, 4.1-10.1) years. Veterans Affairs (VA) and Department of Defense (DoD) administrative data on 1 919 740 veterans from the Long-Term Impact of Military-Relevant Brain Injury Consortium–Chronic Effects of Neurotrauma Consortium were included.ExposureThe main exposure of interest was TBI severity (categorized as mild, moderate or severe [moderate/severe], and penetrating).Main Outcomes and MeasuresThe outcome of interest was the development of brain cancer based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes in either the DoD/VA medical records or from the National Death Index.ResultsAfter 611 107 exclusions (predominately for no encounter during the study period), a cohort including 1 919 740 veterans was included, most of whom were male (80.25%) and non-Hispanic White (63.11%). Median age at index date was 31 (IQR, 25-42) years. The cohort included 449 880 individuals with TBI (mild, 385 848; moderate/severe, 46 859; and penetrating, 17 173). Brain cancer occurred in 318 individuals without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (≤0.06%). After adjustment, moderate/severe TBI (adjusted hazard ratio [AHR], 1.90; 95% CI, 1.16-3.12) and penetrating TBI (AHR, 3.33; 95% CI, 1.71-6.49), but not mild TBI (AHR, 1.14; 95% CI, 0.88-1.47), were associated with the subsequent development of brain cancer.Conclusions and RelevanceIn this cohort study of veterans of the Iraq and Afghanistan wars, moderate/severe TBI and penetrating TBI, but not mild TBI, were associated with the subsequent development of brain cancer.

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Section: Discussionmentioning

confidence: 99%

Traumatic Brain Injury and Subsequent Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars

Stewart,

Howard,

Poltavskiy

et al. 2024

JAMA Netw Open

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“…Philip et al indicated that inflammation, especially TNF-α production, is a tumor promoter in the context of cancer induction [ 25 ]. Ohana et al demonstrated that the transcription factors of the p53, HIF-1a and c-Myc oncogenes play a role in inflammation and in the development of glioblastomas after TBI [ 14 ]. In our previous study, we demonstrated that TBI may activate local and systemic TNF-α production [ 26 – 28 ]; therefore, we speculate that if the inflammatory response continues and becomes chronic in moderate/severe TBI patients, it will persistently activate transcription factors and increase the probability of malignant transformation.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the local effects of a TBI on the brain, TBI may lead to systemic effects by activating neuroinflammation, followed by non-neurological dysfunctions in the cardiovascular system, lungs, liver, gastrointestinal tract, kidneys and neuroendocrine system [ 11 ]. These effects have a similar pathophysiology as carcinogenesis [ 5 – 7 ], especially the local effect of TBI, which may be related to brain tumors, including benign [ 12 ] and malignant tumors [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

New diagnosis of cancer in mild and moderate/severe traumatic brain injury patients in a 12-year population-based study

Nyam

et al. 2022

BMC Cancer

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Background Traumatic brain injury (TBI) has been reported as a risk factor for brain cancer development. However, the magnitude of the impact of TBI on systemic cancer development has not been clarified. Methods A retrospective longitudinal cohort study was conducted using the Taiwan Longitudinal Health Insurance Database between January 2000 and December 2011. A total of 35,306 patients were initially enrolled, and 14,795 patients with mild TBI and 14,795 patients with moderate/severe TBI were matched using the National Health Insurance Research Database in Taiwan. The Cox proportional hazard regression model was used to estimate the hazard ratio (HR) of TBI adjusted for potential confounding factors. Results After matching, the results showed that patients with moderate/severe TBI had a high mortality rate (17.7% vs. 10.4%) and shorter time interval from TBI to death (mean 3.6 years vs. 5.8 years). No differences were observed in cancer incidence (4.1% vs. 4.1%) or risk factors for mortality between mild and moderate/severe TBI patients. However, patients aged between 46 and 55 years, female patients, and patients with pre-existing renal disease had a significant higher cancer incidence risk in moderate/severe TBI compared with mild TBI patients. The top 15 most common cancers showed that mild TBI patients had a higher percentage of head and neck cancer. The overall mortality rate in all TBI patients diagnosed with cancer was about 50%, and the cancer-specific mortality is approximately 85% in death of TBI patients with cancer. Conclusions We concluded that the incidence risk of a new cancer diagnosis and mortality risk of TBI patients with cancer between the mild TBI and moderate/severe TBI patients were not significantly different.

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“…Injury and inflammation have been associated with various types of cancer or other recurrent trauma. However, its implication in GBM development has not been confirmed by epidemiological studies [94].…”

Section: Inflammatory Reaction At Brain Injury Locationmentioning

confidence: 98%

The Association Between Traumatic Brain Injury and Gliomagenesis and Its Special Role in Glioblastoma Multiforme Pathogenesis: A Review

Chrysanthakopoulos

2021

Innovare J Med Sci

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Gliomas are the most common primary and aggressive intracranial tumors, represent 80% of malignant brain tumors, and despite the fact that are relatively rare tumors are responsible for significant mortality and morbidity. Glioblastoma multiforme (GBM) or diffuse astrocytoma, WHO grade IV, is the most common and aggressive primary central nervous system malignancy, represents 45% of all gliomas, shows an average incidence of 3.19/100,000 individuals, its median age of diagnosis is 64 years, and the median survival is 15 months as the 5-year relative survival is 5%. Previous studies have investigated the possible role of genetic and environmental factors in GBM pathogenesis; however, the majority of GBM cases were sporadic and certain risk factors have not been detected. GBM is divided into primary and secondary subtypes which develop through different genetic pathways, affect patients at different ages, and have differences in clinical outcomes, as show a great morphological and genetic heterogeneity. The role of traumatic brain injury (TBI) in GBM formation has been investigated in many previous reports which have hypothesized that TBI may predispose to gliomagenesis; however, the outcomes were highly controversial. Some of those researches have proposed a supposed pathogenesis model that involves a post-traumatic inflammation, stem and progenitor cell transformation, and gliomagenesis. Other similar studies have involved transcription factors associated with TBI such as p53, hypoxia-inducible factor-1a (HIF-1a), and c-Myc. On the other hand, the possibility of a pre-existing tumor rather than a trauma-induced tumor is very possible in such cases.

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Traumatic glioblastoma: commentary and suggested mechanism

Cited by 6 publications

References 22 publications

Traumatic Brain Injury and Subsequent Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars

Traumatic Brain Injury and Subsequent Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars

New diagnosis of cancer in mild and moderate/severe traumatic brain injury patients in a 12-year population-based study

The Association Between Traumatic Brain Injury and Gliomagenesis and Its Special Role in Glioblastoma Multiforme Pathogenesis: A Review

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