BRAIN TUMORS ARE MORE COMMON IN MEN
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 cancer risk,
is significantly less active in male brain cells 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 clinical trials. 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 males and females 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 sex hormones, 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 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."
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."
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