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African- American Prostate
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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 overexpressed 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 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."

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.

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May 22, 1998. Last modified July 5, 1999

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