Traumatic brain injuries linked to risk of brain cancer

Suffering a traumatic brain injury — a staple of combat for U.S. troops in the last two decades — appears to increase the risk of developing brain cancer later in life, a major medical study found.

The study published in JAMA Network Open, an American Medical Association publication, looked at nearly two million post-9/11 veterans with mild, moderate/severe and penetrating traumatic brain injuries or TBIs. 

The findings suggest that veterans experiencing moderate or severe TBIs were 90% more at risk for developing subsequent brain cancer than those who never suffered a TBI while those with penetrating TBIs were more than three times as likely to develop cancer. For veterans with mild cases of TBI – the most common diagnosis – their injuries were not associated with brain cancer later on. 

“The important part of this is that we’re demonstrating that TBI is associated with a wide range of outcomes. We’ve shown cardiovascular disease, now we’ve shown brain cancer and I think that’s important because the simple fact that we know these things allows us to take better care of these folks,” said Ian Stewart, author of the study and professor of medicine at Uniformed Services University. “It informs both DOD and VA care what these patients are at higher risk for.”

As researchers went through medical records, they found that about 450,000 out of 2 million veterans had been diagnosed with TBI at some point. Of those, about 360,000 were mild TBIs while about 64,000 suffered moderate, severe or penetrating trauma.

Within those groups, 80 with mild TBI eventually developed brain cancer, as did 27 with more severe injuries — rates much higher than researchers found among vets who had never been diagnosed with TBI.

Across the U.S., roughly 7 people out of every 100,000 will develop brain cancer. The typical prognosis, the study said, is “poor with a 5-year survival of 35.7%.”

TBI was already associated with long-term health outcomes among veterans with links to cardiovascular disease, dementia, epilepsy and poor mental health, according to researchers. Some work has even linked TBIs to increased risk of suicide, Stewart said. 

“The more severe the TBI, the more likely you are to have these outcomes. But even mild TBIs can put you at risk for these things,” Stewart said. 

“While the absolute number of brain cancer diagnoses was small, these diagnoses are associated with profoundly poor outcomes,” researchers said. “Given that TBI is a common injury incurred in the course of military service, further research of this rare but devastating condition is needed to better identify those at risk and develop screening protocols.”

According to a 2022 Traumatic Brain Injury Center of Excellence report, more than 468,000 U.S. troops suffered first-time TBIs in the two decades of war in Iraq and Afghanistan. However, TBIs continue to persist among service members with the majority of cases found in the Army. In the first quarter of 2023, the DOD recorded 8,390 TBIs with 85% of cases classified as mild.

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The study, first reported by Military.com, was funded by the Assistant Secretary of Defense for Health Affairs and the Department of Veterans Affairs.

The research comes amid a new spike in troops suffering TBIs in combat. More than 150 attacks by Iranian-backed militias using rockets, drones and ballistic missiles have struck bases manned by U.S. troops in Iraq and Syria. Dozens of troops have suffered TBIs since the attacks began in mid-October.

“Very little is known about the association between exposures and subsequent brain cancer risk, with the exception of ionizing radiation, which has been established to increase risk,” the study’s authors wrote.

The study also notes that current evidence examining the connection between TBI and subsequent brain cancer is “conflicting” with some research suggesting an association and others finding none.

Stewart said their original hypothesis was that there would be a linkage because a TBI causes inflammation and “inflammation has been postulated to be one of the potential things that can cause brain cancer,” he said. 

Though the statistical results were strong, researchers cautioned that the make-up of the study was necessarily narrow and might not be applicable to a wider population. Troops covered in the study were 80% male with a median age of 31 years old, majority White, non-hispanic and mostly from the enlisted ranks.

Results for women, as an example, were not broad enough to draw a strong conclusion.

“There was an insufficient number of events in female patients to conduct a stratified analysis based on sex,” the report said.

Other studies have also found that women have generally not been well represented in TBI research on service members and veterans. Some evidence suggests that female veterans with TBI are more frequently diagnosed with depression and use more outpatient services than their male counterparts.

“It just wasn’t something that we could look at but that’s a very important point, because the next war will be different than the last one so we’re going to see a lot more female casualties and it’s important now to try to get a sense of what those long term outcomes are going to be,” he said.

Definitions of TBI levels

Researchers used the following definitions to look at TBI links to brain cancer.

Mild TBI/concussion: characterized by a confused or disoriented state lasting less than 24 hours; or loss of consciousness for up to 30 minutes; or memory loss that lasts less than 24 hours. A computed tomography scan is not indicated for most patients with a mild TBI. If obtained, it is normal.

Moderate TBI: characterized by a confused or disoriented state which lasts more than 24 hours; or loss of consciousness between 30 minutes and 24 hours; or memory loss that lasts between 24 hours and seven days; or meets criteria for mild TBI except an abnormal CT scan is present. Excludes penetrating TBI. A structural brain imaging study may be normal or abnormal.

Severe TBI: characterized by a confused or disoriented state which lasts more than 24 hours; or loss of consciousness for more than 24 hours; or memory loss lasting more than one week. Excludes penetrating TBI. A structural brain imaging study may be normal but usually is abnormal.
Penetrating TBI (or open head injury): consists of a head injury where the scalp, skull and dura mater (the outer layer of the meninges) are penetrated. Injuries can be caused by high-velocity projectiles or lower velocity objects like knives, or home fragments from a skull fracture which are driven into the brain.

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