Traumatic Brain Injury and Risk of Malignant Brain Tumors in Civilian Populations.

IMPORTANCE

A 2024 US study reported that veterans of the Iraq and Afghanistan wars affected by traumatic brain injury (TBI) had an increased risk of developing brain tumors. However, studies among civilians have shown conflicting results and have not replicated the association between TBI and brain tumor risk.

OBJECTIVE

To examine whether history of TBI in US adult civilians is associated with a risk of subsequent development of malignant brain tumors.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from a tertiary academic medical center (Mass General Brigham [MGB]) patient data registry encompassing January 1, 2000, to January 1, 2024. Adult patients (aged >18 years) with mild TBI or moderate to severe TBI (exposure group) were compared with an age- and sex-matched group without a history of TBI (control group). The MGB data were compared across the same time span with data from 2 other tertiary academic medical centers (University of California [UC] Health Data Warehouse and Northwestern Medicine).

EXPOSURE

TBI, which was categorized by severity as mild or moderate to severe.

MAIN OUTCOMES AND MEASURES

The primary outcome was development of malignant brain tumor based on International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) diagnostic codes in the patient data registry of each cohort. Cox proportional hazards regression analysis was used to determine whether TBI was associated with brain tumor development. The MGB results were then meta-analyzed with the UC Health and Northwestern Medicine data.

RESULTS

The MGB cohort included 151 358 adults: 75 679 control participants (51.8% female; median age, 56 years [IQR, 39-71 years]) and 75 679 civilians with TBI. Of the civilians with TBI (median age, 56 years [IQR, 39-74 years]), 60 735 had mild TBI (54.7% female; median age, 54 years [IQR, 37-73 years]) and 14 944 had moderate to severe TBI (42.1% female; median age, 64 years [IQR, 47-79 years]). The median follow-up duration for the MGB cohort was 7.2 years (IQR, 4.1-10.1 years). Malignant brain tumor prevalence was 0.6% in the moderate to severe TBI group vs 0.4% in the control and mild TBI groups. The moderate to severe TBI group had a higher risk of developing malignant brain tumors (hazard ratio [HR], 1.67 [95% CI, 1.31-2.12]) compared with the mild TBI group (HR, 0.99 [95% CI, 0.83-1.18]). The risk persisted when meta-analyzed with data from the other 2 centers (HR, 1.57 [95% CI, 1.26-1.95]).

CONCLUSIONS AND RELEVANCE

In this cohort study of US adult civilians, a history of moderate to severe TBI was associated with risk of developing malignant brain tumors. This association was confirmed in a meta-analysis with geographically diverse sites across the US. Additional research is needed to clarify the mechanism through which TBI increases the risk of developing brain tumors.