Grant to fund African American prostate cancer studies

The National Cancer Institute has awarded investigators at the Winship Cancer Center $1.2 million over four years to establish an institution-wide, multidisciplinary research program in prostate cancer. It will fund four different pilot projects aimed at African American and medically underserved populations in the Southeast. By revealing how environmental, hormonal, genetic and nutritional factors may affect an individual's risk for prostate cancer, these projects will enable scientists in basic, clinical and cancer control research to collaborate in bringing new therapies quickly from the lab to patients.

African Americans have the highest incidence rate in the world for prostate cancer. The death rate for blacks from this disease rose by 35 percent between 1973 and 1990. For all men, it is second only to lung cancer as a cause of cancer-related deaths. Compared to whites, black men are diagnosed at later stages and have worse survival rates, even when diagnosed early. The reasons for these racial differences remain unknown.

Sam Graham Jr., professor of surgery and chief of the Section of Urology, is the principal investigator and program director for the study. "This exciting new research has the potential to make a significant and lasting impact on reducing both incidence and mortality of prostate cancer," he said. "We are particularly eager for this opportunity because we see such a large number of prostate patients at Winship."

In the first pilot project, epidemiologists will assess how agricultural exposures and dietary intake among rural African Americans relate to prostate cancer risk. Previous occupational studies show risk to be strongly associated with exposures related to farming, particularly work with herbicides and poultry. Both are extremely prevalent in Georgia. Intake of fat and antioxidants may also be independently associated with prostate cancer risk, though few dietary studies have been conducted among the African American population. A questionnaire will be developed to determine common dietary practices of this group.

The second pilot study will help determine the effect of specific alterations in mitochondrial DNA on prostate cancer development in African Americans, an idea based on genetic research conducted at the Winship Cancer Center. Oxygen free-radical damage to mitochondrial DNA is thought to be a major factor in cellular aging and cancer. Specific mutations serve as inheritable factors that may predispose this population to develop prostate cancer. This study will identify the African American lineages that have the highest risk of developing the disease, making it easier and more efficient to monitor these individuals.

The third project will study racial differences in levels of an androgen hormone called alpha-5 reductase, found in the prostate. This hormone leads to higher concentrations of the more potent androgen, dihydrotestosterone (DHT). The development of prostate cancer is dependent on stimulation by these androgens. Follow-up studies will also look at enzymes involved in the inactivation of DHT, and at other androgen metabolites such as estradiol, which may be important in prostate cancer progression.

In another look at genetic markers, the fourth pilot project will investigate an alteration, or polymorphism, of a gene that produces an enzyme called PADPRP (poly ADP ribose polymerase). PADPRP is needed to repair naturally-occurring breaks in DNA and to control cell growth. Malignant cells are characterized by their failure to regulate these two important processes properly. If the PADPRP gene is somehow altered, breaks in DNA are not repaired and faulty DNA is produced, resulting in cancer. The pilot project will help determine if African American men have a higher frequency of polymorphisms for this gene than do other populations. The information will help establish the value of this genetic marker to identify higher-risk populations among blacks. These subgroups could then be targeted for screening programs and possibly more aggressive therapies.

Howard Ozer, co-principal investigator of the study and director of the Winship Cancer Center, said the study could have important implications for prostate cancer prevention and therapy in African Americans. "The grant will help us establish an interdisciplinary group to address the continuum of research including etiology, risk factors, pathology, therapy, progression and prognostic tools," he said.

-- Kate Egan

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