Big brains amplify glioma risk
Intracranial volume, a proxy measurement for brain size, appears to be a strong predictor of the risk of high-grade glioma especially in women, according to a recent study.
“Assuming that the number of cell divisions is related to organ size, our findings are a clinical example supportive of the controversial ‘bad luck’ theory, which claims that development of cancer often results from a lottery of random mutations in normal stem cells, with important implications in our understanding of cancer aetiology,” said researchers.
Using contrast-enhanced 3D T1-weighted cerebral magnetic resonance imaging (MRI), researchers measured the intracranial volume of 124 high-grade glioma patients and 995 general population controls. Those who had undergone previous intracranial surgeries and with Chiari malformation were excluded.
Majority of the glioma patients were male (60.5 percent; n=75; mean age 52.9±4.5 years), in whom the mean intracranial volume of 1,781±129 mL. This was 92-mL larger than male controls (47.7 percent; n=471; mean age 59.2±4.2 years), whose mean intracranial volume was 1,689±122 mL. The difference achieved statistical significance (p<0.001). [Neurooncology 2018;20;1225-1230]
Similar findings were observed for females. Those with high-grade glioma (39.5 percent; n=49; mean age 59.7±5.1 years) had a mean intracranial volume of 1,537±130 mL, which was significantly higher than that in general-population controls (52.3 percent; n=524; mean age 58.7±4.3 years; 1,482±114 mL; p=0.001).
These findings were further confirmed through binomial logistic regression analysis. For every 100-mL increase in intracranial volume, there was an associated 69-percent jump in the risk of high-grade glioma (odds ratio [OR], 1.69; 95 percent CI, 1.44–1.98; p<0.001).
Sex was also an important factor, such that males were 44-percent less likely than females to develop the malignancy (OR, 0.56; 0.33–0.93; p=0.026). The interaction between intracranial volume and sex had no meaningful effect on the model and was thus omitted.
“After adjusting for [intracranial volume], male sex was associated with lower risk of high-grade glioma, suggesting that the known higher incidence in men is explained by the sex difference in brain volumes,” researchers explained.
“One could speculate that the declining risk in the oldest age groups might in part be explained by the age-dependent atrophy that reduces the number of cells at risk, but there is also a risk of underdiagnosing high-grade glioma in the highest age group due to increased comorbidity,” they continued.
It is however interesting to view the present findings in light of a recent study that showed a reduced risk of glioma in the years immediately after an acute brain injury, researchers added. “It is possible that the cell death and atrophy following traumatic brain injury reduce the risk of glioma by a reduction of cells at risk.” [Neuro Oncol 2015;17:718-724; Neuroimage Clin 2014;5:128-140]
The present study is the first to the investigate role of brain size in high-grade glioma development, researchers said. But two previous reports have demonstrated links to other factors such as height and socioeconomic status, which are both in turn associated with brain volume. [Int J Epidemiol 2012;41:1075-1085; Cereb Cortex 2001;11:816-824]
“Thus, brain volume may be an important underlying factor for many previously reported risk factors, changing our understanding of the disease. This has implications for future research on the aetiology of glioma, and the presented organ volume approach may be of interest for studying other cancers as well,” said researchers.