Baltimore,
MD (10/8/98)- The discovery of the first major cancer gene on the human
X chromosome could be an important step in the battle against prostate
cancer, report Johns Hopkins researchers.
Working in collaboration with researchers in the United States, Sweden
and Finland, the investigators localized a a gene conferring susceptibility
to prostate cancer to a narrow region on the X chromosome. This gene is
believed to be responsible for approximately 16% of all hereditary prostate
cancer cases.
"This is clearly a major step toward understanding the factors that
lead to prostate cancer. We're still at the early stages in figuring out
genetic involvement in prostate cancer, but this finding is real progress,"
said Patrick C. Walsh, M.D., Urologist-in-Chief, Johns Hopkins University.
The researchers painstakingly compared genetic information from members
of prostate cancer families and normal people, looking for anomalies that
might point to the culprit cancer gene. After studying more than 1,000
people, they determined that a new gene locus, called HPCX (for human prostate
cancer on the X chromosome), was strongly implicated in 15 to 20 percent
of inherited forms of the diseases.
"Mapping HPCX brings us one step closer to understanding the origins
of prostate cancer, at least in some families," says Francis Collins, M.D.,
director of the National Human Genome Research Institute.
Geneticists have long suspected that the X chromosome might be involved
in the development of prostate cancer. Family studies had shown that a
man's risk of prostate cancer is higher if his brother had prostate cancer
than if his father had the disease. This suggested a genetic trait carried
on the X chromosome, passed from mothers to sons.
"Finding genes for prostate cancer is particularly difficult, because
it's hard to separate populations of people who get the disease due to
a strong-acting mutant gene from those who have it from other causes such
as, say, interactions between the environment and less influential genes.
You can have one family where four brothers have prostate cancer but only
three have the HPCX gene," said Dr. William Isaacs, Department of Urology,
Johns Hopkins University.
In a few rare diseases, such as ataxia
telangiectasia, geneticists have been able to identify a single gene
that appears to cause disease. However, in more common diseases such as
cancers of the breast, it is clear that many genes are involved. This is
believed to be the case with prostate cancer. Indeed, the same team of
researchers that uncovered HPCX identified the location of the first
specific gene that predisposes men to develop prostate cancer two years
ago. That gene HPCI (hereditary prostate cancer 1) is located in on a region
of chromosome 1, one of 22 pairs of non-sex human chromosomes.
The next step will be to isolate the precise gene associated with the
HPCX locus. This could lead to the development of new diagnostic and therapeutic
approaches to the disease. The researchers may have an easier time finding
the HPCX gene than they did HPCI, because more is known about the sequence
and arrangement of genes on the X chromosome and because it is easier to
follow the inheritance of a gene on a sex chromosome.
Prostate cancer causes more than 35% of all cancer cases affecting
men. Of the approximately 200,000 new cases diagnosed in the U.S. each
year, an estimated 10 percent are inherited.
The research is reported in the October 1998 issue of Nature Genetics.
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