Genetic Theories

Besides having the highest rates in the USA, African American men suffer the highest incidence rate of prostate cancer in the world. It has been postulated that these findings may be due to a genetic predisposition of African Americans to the development of this disease. Thus far, studies have been unable clearly to identify a gene or genes responsible for the development of prostate cancer. It appears that, whatever genetic predisposition there exists for prostate cancer, there also exists a concomitant environmental factor responsible for the development of neoplasia.

Studies looking for possible genetic causes have demonstrated linkage to the site of the HPC-1 (human prostate cancer) gene, mapped to 1q 24-25. This locus is associated with an increased risk of developing the hereditary form of prostate cancer. This finding was first noted by Issacs and colleagues in 1996.19 Linkage analysis revealed that 34% of 66 North American pedigrees where three or more men were affected by prostate cancer were linked to the HPC gene. These studies suggest that derangements in this gene may be associated with up to one-third of hereditary prostate cancer cases, which amounts to only about 3% of total prostate cancer cases.20

Subsequently, additional linkage studies have been per-formed.21 Studies by Thibodeau etal.,22 Eeles etal.23 and McIndoe etal.24 failed to demonstrate the same linkage to the HPC-1 gene locus in families with hereditary prostate cancer seen in Issacs' work. Further studies on linkage to HPC-1

demonstrated that positive linkage was seen in African American families with the age of onset greater than 65 years of age. It appears in these studies that African Americans disproportionately contribute to the finding of positive linkage. The linkage studies to HPC-1 thus far undertaken have shown marginal evidence for linkage to this site. None the less, the strongest evidence comes from the African American community.

Another avenue of interest in the study of prostate cancer has been the effect of circulating androgens. Testosterone and its most active metabolite, dihydrotestosterone, are the principal steroid hormones involved in the growth and development of the prostate gland. Serum levels of these hormones have

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