A significant protein that lowers the risk of cancer is less active in men, which explains why they're at a higher risk of brain tumor than women, a new study finds.
It is an established fact that men are at a higher risk of brain tumor than women. In a new study, researchers from Washington University found that retinoblastoma protein (RB), a protein known to reduce cancer risk, is significantly less active in male brain cells than in females.
"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," said senior author Joshua Rubin in a press statement. "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."
Researchers are now developing drugs that affect this protein so that it trigger's its anti-tumor characteristics, allowing cancer patients to live longer.
"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."
Rubin and his team said that while there are many gender-related diseases which have been associated with sex hormones, these hormones could not account for the 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," he 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."
After a series of genetic alterations and exposure to a growth factor, researchers found that male brain cells became cancerous faster and more often than female brain cells. They also noted that RB was more likely to be inactivated in male brain cells than in female brain cells. When they disabled the RB protein in female brain cells, the cells were equally susceptible to becoming cancerous.
"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 current study was published online in The Journal of Clinical Investigation. The project was supported by the National Institutes of Health and the Children's Tumor Foundation Young Investigator Award.
