|
| |
bcl-2 Gene Linked to
Prostate Cancer in African Americans
May 21 1998. A gene
that blocks cells from dying may play a role in prostate cancer in African
Americans. Researchers say this would help explain why black men have the
highest rate of prostate cancer in the world. The findings, by medical
researchers at University of California, Davis appeared in the June 1998 issue
of the Journal of Urology.
These finding underscore the importance of screening for African-American men,
say Dr. Ralph W. deVere White, director of the UC Davis Cancer Center, and his
co-author Dr. Aaron Jackson, Chief of Urology at Howard University.
Even More Need for
Early Detection
More than 300,000 men are diagnosed with prostate cancer each year, and more
than 40,000 a year die from the disease. Warning signs for advancing prostate
cancer include inability to urinate, blood in the urine, and pain or burning
during urination. But the disease starts without any symptoms. "In its
early stages, prostate cancer is silent," says Dr. Jackson. "A person
cannot make a diagnosis of prostate cancer on themselves based on
symptoms."
As a result, these researchers say, African American men and those who have a
family history of prostate cancer need a physical exam and a prostate-specific
antigen (PSA) test when they turn 40, and from then on annual check ups. The
American Cancer Society agrees.
The-encouraging news from the study, says deVere White, is that "if these
cancers are detected while they are very small, there is no difference in
survival rates between black and whites. And the overall cure rate for prostate
cancer caught in its earliest stages is greater than 90 percent." More work
is needed, they say, to find out if and how bcl-2 interacts with other genes.
Could Explain
Vulnerability
"African-American men develop prostate cancer earlier and in a more
aggressive form than any other ethnic group," says deVere White. "They
are more likely to die from the disease and more frequently have a recurrence
after treatment with radical prostatectomy, the surgical removal of the prostate
gland. Even when consideration is given to diet, lifestyle, or socioeconomic
factors, the differences in the behavior of prostate cancer between the races
remains unexplained."
bcl-2 Stops Damaged
Cells from Dying Off
The research suggests that the difference in aggressiveness of prostate cancer
in African Americans may lie in altered expression of bcl-2, a gene that plays a
central role in preventing cells from dying.
In all cells, one set of genes tells the cell to do the normal cell cycle of DNA
replication and cell division. A separate (linked) set of genes switches on
apoptosis (programmed cell death) at the right time. Apoptosis is both a natural
part of cell aging and a means of killing off cells whose DNA has been damaged.
Cancers can grow by an increase in cell proliferation; by decrease in apoptosis,
or both.
In prostate cancer, the gene bcl-2 acts as a major block to cell death. The
researchers evaluated four markers of tumor aggressiveness in cancerous
prostates from 43 black and 74 Caucasian men to see if any of these markers were
related to racial differences. The markers are:
· DNA ploidy,
which shows the number of extra chromosomes in the nucleus
·
Proliferation, the degree of tumor growth
· p53, a gene
that is over expressed in many cancers and predicts tumor progression
· bcl-2, a gene
that blocks cell death.
The researchers
found a connection between bcl-2 levels and the more aggressive prostate cancer
tumors from black men. They also found both low-and high-grade black prostate
tumors had similar DNA ploidy distributions, rather than a higher degree of
abnormality for the high-grade tumors as would be expected.
These results suggest that in African Americans "tumor growth is more rapid
because fewer cells are instructed to die," says deVere White. "With
the bcl-2 gene over expressed, it causes prostate cancer cells to flourish when
they would normally perish." And "if programmed cell death is blocked,
metastasis could occur earlier in the course of the disease."
|
Companies Already
Developing Drugs
The bcl-2 gene
inhibits apoptosis (programmed cell death) of cancerous cells. The protein
produced by this gene has two known critical functions in the progression
of cancer:
· It
makes cancer cells immortal, creating a survival advantage of
malignant over normal cells
· It
confers resistance to radiation and chemotherapy, rendering these
treatments ineffective in the late stages of many types of cancers
The bcl-2 gene
is believed to be important in prostate cancer as well as in non-Hodgkin's
lymphoma, breast, lung and colon cancers. Drugs for targeting bcl-2 in
order to stop its cancer-promoting functions have already been patented. |
The study was done
at three centers - UC Davis School of Medicine and Medical Center; Howard
University in Washington, D.C., and the Northern California Cancer Center in
Union City, Calif. The research was funded by a public health grant from the
National Institutes of Health.
|
