Study reveals one reason brain tumors are more common in men

August 1, 2014
Study reveals one reason brain tumors are more common in men
Reduced levels of an anti-cancer protein make male brain cells more vulnerable to becoming tumors, according to a new study at Washington University School of Medicine in St. Louis. Credit: Robert Boston

New research at Washington University School of Medicine in St. Louis helps explain why brain tumors occur more often in males and frequently are more harmful than similar tumors in females. For example, glioblastomas, the most common malignant brain tumors, are diagnosed twice as often in males, who suffer greater cognitive impairments than females and do not survive as long.

The researchers found that retinoblastoma protein (RB), a protein known to reduce , is significantly less active in male than in female brain cells.

The study appears Aug. 1 in The Journal of Clinical Investigation.

"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, MD, PhD. "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."

Rubin noted that RB is the target of drugs now being evaluated in . Trial organizers hope the drugs trigger the protein's anti-tumor effects and help cancer patients survive 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 and separately in clinical trials."

Scientists have identified many sex-linked diseases that either occur at different rates in males and females or cause different symptoms based on sex. These distinctions often are linked to , which create and maintain many but not all of the biological differences between the sexes.

However, Rubin and his colleagues knew that sex 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 in males and females at puberty. But they don't happen then or later in life when menopause changes female sex hormone production."

Rubin used a cell model of glioblastoma to prove it is easier to make male brain cells become tumors. After a series of genetic alterations and exposure to a growth factor, male brain cells became cancerous faster and more often than female brain cells.

In experiments designed to identify the reasons for the differences in the male and female cells, the team evaluated three genes to see if they were naturally less active in male brain cells. The genes they studied—neurofibromin, p53 and RB—normally suppress cell division and cell survival. They are mutated and disabled in many cancers.

The scientists found 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 cancers.

"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."

Explore further: Brain anatomy of dyslexia is not the same in men and women, boys and girls

More information: Sun T, Warrington NM, Luo J, Brooks M, Dahiya S, Snyder SC, Sengupta R, Rubin JB. Sexually dimorphic RB inactivation underlies mesenchymal glioblastoma prevalence in males. The Journal of Clinical Investigation, online Aug. 1, 2014.​

Related Stories

Gender influences symptoms of genetic disorder

February 7, 2014

(Medical Xpress)—A genetic disorder that affects about 1 in every 2,500 births can cause a bewildering array of clinical problems, including brain tumors, impaired vision, learning disabilities, behavioral problems, heart ...

Progesterone could become tool versus brain cancer

June 19, 2014

(Medical Xpress)—The hormone progesterone could become part of therapy against the most aggressive form of brain cancer. High concentrations of progesterone kill glioblastoma cells and inhibit tumor growth when the tumors ...

Recommended for you

Flu study, on hold, yields new vaccine technology

September 2, 2015

Vaccines to protect against an avian influenza pandemic as well as seasonal flu may be mass produced more quickly and efficiently using technology described today by researchers at the University of Wisconsin-Madison in the ...

We've all got a blind spot, but it can be shrunk

August 31, 2015

You've probably never noticed, but the human eye includes an unavoidable blind spot. That's because the optic nerve that sends visual signals to the brain must pass through the retina, which creates a hole in that light-sensitive ...

Biologists identify mechanisms of embryonic wound repair

August 31, 2015

It's like something out of a science-fiction movie - time-lapse photography showing how wounds in embryos of fruit flies heal themselves. The images are not only real; they shed light on ways to improve wound recovery in ...

New 'Tissue Velcro' could help repair damaged hearts

August 28, 2015

Engineers at the University of Toronto just made assembling functional heart tissue as easy as fastening your shoes. The team has created a biocompatible scaffold that allows sheets of beating heart cells to snap together ...

Fertilization discovery: Do sperm wield tiny harpoons?

August 26, 2015

Could the sperm harpoon the egg to facilitate fertilization? That's the intriguing possibility raised by the University of Virginia School of Medicine's discovery that a protein within the head of the sperm forms spiky filaments, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.