Genetic Analysis of Hereditary Prostate Cancer

Molecular approaches to the understanding of human neoplastic disease have revealed that
multiple genetic alterations are an essential component of tumorigenesis. Both germline and
somatic genetic alterations can be involved in the malignant transformation of normal cells.
Identification of the genes involved in neoplastic transformation has been approached through
the molecular analysis of sporadic cancers and the genetic study of families with an
inherited predisposition for cancer. The interplay of these two approaches has led to the
characterization of genes such as the retinoblastoma (Rb) gene, the p53 gene and the
adenomatous polyposis coli (APC) gene that are all involved in the development of both
hereditary and non-hereditary forms of cancer. Inherited mutations in such genes predispose
affected families to hereditary cancer syndromes, affording an opportunity to identify
genetic lesions that also cause the more common sporadic cancers.

Prostate cancer (PRCA) is the most common cancer diagnosed (1999 estimate 179,300 cases) and
the second leading cause of cancer mortality (1999 estimate 37,000 deaths) in men in the
United States. Family history is the single strongest risk factor currently known for
prostate cancer. This raises the possibility that heritable genetic factors may be involved
in the development of this disease in a subset of men. The genetic contribution to diseases
of complex origin such as cancer is often most salient in families of early onset cases.
Therefore, prostate cancer inheritance following a simple Mendelian pattern may be identified
in the families of probands with early-onset cases. Common susceptibility alleles of small
effect may be detectable in families with later-onsent and/or less strong family history of
PRCA or in case-control data.