Do Bigger Brains Contribute to More Cancer?

Intracranial volume strongly predicts high-grade glioma, according to a recent study published in Neuro-Oncology.

“Assuming a positive correlation between the number of stem cell divisions in an organ and size of the same organ, we hypothesized that variation in intracranial volume, as a proxy for brain size, may be linked to risk of high-grade glioma,” wrote the authors.

The etiology of glioma is largely unknown. Researchers have yet to elucidate many risk factors for high-grade glioma, despite extensive epidemiologic study. To date, only age, male sex, ionizing radiation, Caucasian ethnicity, and some rare hereditary syndromes have been implicated.

A controversial recent study found that cancer risk is positively correlated with organ stem cell divisions, with tissues exhibiting more stem cells tied to a higher cancer risk due to increased chance. Of note, gliomas are thought to originate from glial stem cells. Organ size and cancer risk tend to increase with height; thus, men, who have larger brains, have been shown to demonstrate a higher risk of glioma.

In the current population-based case control study, researchers examined the relationship between intracranial volume (ICV) and the risk of high-grade glioma. They also controlled for ICV to examine the role that sex plays in glioma risk.

ICV was calculated based on pretreatment 3D T1-weighted MRI brain scans from 124 high-grade glioma patients and 995 controls from the general population. They used binomial logistic regression to determine the effect of ICV and sex on high-grade glioma risk.

The team found that an increase in ICV of 100 mL was correlated with an odds ratio of high-grade glioma of 1.69 (95% CI, 1.44‒1.98; P < .001). After adjusting for intracranial volume, female sex was identified as a “risk factor” for high-grade glioma (odds ratio for male sex, 0.56; 95% CI, 0.33‒0.93; P = .026).

The researchers were surprised to find that, after adjusting for ICV, there was a lower risk of high-grade glioma in men than in women. They suggested that this result could stem from merely controlling for ICV, which could lead to over- or under-adjustment for the effects of sex.

“After adjusting for ICV, 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,” wrote the authors. “Our results are in line with the recent and controversial ‘bad luck’ theory, which posits that development of cancer to a large part results from a lottery of random mutations that occur during DNA replication in normal stem cells, and hence number of cell divisions and, indirectly, organ size are major risk factors for cancer.”

Despite the intriguing nature of the results, Henry Brem, MD, director of the department of neurosurgery at the Johns Hopkins Medicine, is unsure of the relevance of the Fyllingen et al study. “The authors hypothesized that larger brain size is associated with a higher likelihood of cancer and demonstrated the association,” he said. “I’m not sure that the data verify that it is a [risk factor]. It is an association, not necessarily a risk factor.”