African- American Prostate
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.
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.
"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."
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
- DNA ploidy, which shows the number of extra chromosomes in the nucleus
- proliferation, the degree of tumor growth
- p53, a gene that is overexpressed in many cancers and predicts tumor
- 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 overexpressed,
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."
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
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.
May 22, 1998. Last modified July 5, 1999
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