No significant differences were seen in the frequency of TBI between the brain-cancer groups and their matched controls (OR, 0.83 for all verified central nervous system tumors; OR, 1.34 for all gliomas).

Zampieri et al. (1994) conducted a case–control study to assess risk factors related to brain tumors in 195 patients who presented with confirmed cerebral glioma in four neurosurgical departments in Italy. Controls were matched to cases on age, sex, date of hospitalization, and residence. A structured questionnaire was administered to assess education, occupation, environmental exposures, medical history, and history of TBI. TBI was classified as mild if LOC was brief and severe if LOC lasted for over 1 hour, and there were any related neurologic deficits, epilepsy, cranial fracture, or any neurologic procedure. The authors found no statistically significant association between malignant astrocytomas and history of TBI (OR, 0.5; 95% CI, 0.2–1.3). The study was limited in that there was a potential for substantial recall bias.


The committee reviewed 14 primary studies and two secondary studies of TBI and brain tumors and found mixed results. The three large population-based registry studies in Minnesota, Denmark, and Sweden found no association between TBI and risk of brain tumors, although the Danish study almost reached statistical significance. The Minnesota study was able to ascertain exposure up to 44 years earlier, and there were more than 3.2 million person-years of followup in the Swedish study. However, there is evidence from some of the other studies that there may be a weak but significant association between TBI and meningioma and that risk of brain tumors may be increased 10 years or more after TBI; this suggests the possibility of a long latent period before clinical presentation. The committee therefore does not believe that the possibility of an association between TBI and risk of later brain tumors is a closed question. It believes that longer-term followup, especially in large registry-based studies, is warranted to understand where there is measurable risk and, if it is increased, when and with what types of tumors it is most likely to be observable. For now, however, the committee concludes that the inconsistent results of the studies are most supportive of a classification of inadequate/insufficient evidence to determine whether an association exists.

The committee concludes, on the basis of its evaluation, that there is inadequate/insufficient evidence to determine whether an association exists between moderate or severe TBI and subsequent development of a brain tumor.

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