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MOLECULAR EPIDEMIOLOGY OF PROSTATE CANCER IN TOBAGONIANS

Principal Investigator: BUNKER, CLAREANN H

Preliminary prostate cancer screening data from the Afro- Caribbean population aged 50-79 on the Caribbean island of Tobago revealed a high rate (29 percent) of elevated PSA (greater than 4ng/ml). Of the 79 percent undergoing biopsy, 51 percent were diagnosed with prostate cancer. High incidence of prostate cancer has recently been reported among Afro-Caribbean Jamaicans. These data suggest that the elevated risk for prostate cancer, observed in African Americans, is present in other populations of West African descent. This strongly suggests that prostate cancer risk is influenced by genetic component(s) in combination with lifestyles/metabolic factors common across populations of African descent living in diverse environments. We propose to conduct a molecular epidemiology study of prostate cancer in the Tobago male population, aged 40-79 (n=5121), (92 percent of African descent). This proposed study will screen men aged 40-49 (n=1800) for elevated PSA (greater than 2ng/ml) or abnormal DRE, in addition to men aged 50-79. We expect to study 300 screening detected cases compared with 300 frequency age matched controls. We will determine whether variants in candidate genes related to sex hormone metabolism, growth factor, vitamin D, PSA transport and toxic substance metabolism, or to loci for familial prostate cancer of chromosomes 1 and X, are associated with prostate cancer, and whether gene frequencies differ from published studies of Caucasian and African American populations. Other molecular markers will include serum arachidonic acid and IGF-1 (for each, hypothesize high levels in cases). Bone mineral density, a surrogate for long term IGF-1 and sex hormone exposure, and central fat distribution will be measured (for each, hypothesize elevated in cases). This large, very cooperative, male population of West African descent, provides a unique opportunity for the study of prostate cancer risk because prostate cancer risk is high, the population is primarily of West African descent, and there is less admixture than among African Americans. Understanding the contribution of environment, genetic and metabolic factors will lead to measures to reduce the risk for prostate cancer among men of West African descent in the U.S., the Caribbean and other geographic areas.

ADULT AIDS CLINICAL TRIALS UNIT

Principal Investigator: MELLORS, JOHN W.

This application is for a new Adult AIDS Clinical Trials Unit (AACTU) in Pittsburgh as part of the Adult AIDS Clinical Trials Group (AACTG). The Pittsburgh Unit joined the AACTG in January 1997, by becoming a subunit of the Case Western Reserve University AACTU. Because of performance as a subunit and contributions to the scientific agenda of the AACTG, the Executive Committee recommended that the Pittsburgh Unit become a new AACTU in the next funding cycle (2000-2004). The Pittsburgh AACTU plans to enroll 360 patients into AACTG trials between 2000-2004 (60 patients year 1; 75 patients per year for years 2-5). This is well within the capacity of the Unit, which has over ten years of experience conducting NIH- and industry sponsored clinical trials in HIV-infected adults, including women and minorities. The establishment of an AACTU in Pittsburgh will permit several HIV researchers at the University of Pittsburgh to contribute to the scientific agenda of the AACTG. Under the leadership of the Principal Investigator, John W. Mellors, M.D., the research plan of the Pittsburgh Unit will concentrate on the following areas of the AACTG scientific agenda: (1) HIV Disease - identification of effective "rescue/salvage" therapies and evaluation of HIV drug resistance testing; (2) Infectious Complications - treatment and prophylaxis of opportunistic infections; (3) Immunology/immune-based Therapies - mechanisms of immune reconstitution and therapeutic vaccines; (4) Metabolic Complications - the effects of antiretroviral therapy on glucose metabolism, insulin sensitivity and body composition; (5) Neurologic Complications - neuropathogenesis of CNS HIV infection and the effects of treatment; (6) Longitudinal Linked Randomized Trials - virologic factors that predict drug failure; and (7) Pharmacology - distribution/interaction of antiretrovirals and interventions to enhance medication adherence.




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