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Men are twice as likely to develop brain tumors because an anti-cancer protein is significantly less active in male brains.

Statistics show that men are significantly more likely to be diagnosed with brain tumor. For instance, some common malignant brain tumors called glioblastomas are diagnosed twice as often in men. What's more, men who suffer glioblastomas experience more cognitive impairments and have a lower survival rate than their female counterparts.

New research reveals that the retinoblastoma protein (RB), a protein known to lower cancer risk, is significantly less active in male neurons than in female neurons.

"This is the first time anyone ever has identified a sex-linked difference that affects tumor risk and is intrinsic to cells, and that's very exciting," senior author Joshua Rubin, MD, PhD, said in a news release. "These results suggest we need to go back and look at multiple pathways linked to cancer, checking for sex differences. Sex-based distinctions at the level of the cell may not only influence cancer risk but also the effectiveness of treatments."

"In clinical trials, we typically examine data from male and female patients together, and that could be masking positive or negative responses that are limited to one sex," said Rubin, who is an associate professor of pediatrics, neurology and anatomy and neurobiology. "At the very least, we should think about analyzing data for males and females separately in clinical trials."

While these differences are often linked to sex hormones, researchers said that sex hormones are not responsible for the sex differences in brain tumor risk.

"Male brain tumor risk remains higher throughout life despite major age-linked shifts in sex hormone production in males and females," Rubin said. "If the sex hormones were causing this effect, we'd see major changes in the relative rates of brain tumors in males and females at puberty. But they don't happen then or later in life when menopause changes female sex hormone production."

"There are other types of tumors that occur at different rates based on sex, such as some liver cancers, which occur more often in males," Rubin said. "Knowing more about why cancer rates differ between males and females will help us understand basic mechanisms in cancer, seek more effective therapies and perform more informative clinical trials."

The findings are published in The Journal of Clinical Investigation.