The Genes That Cause Prostate Cancer:
What We Know So Far

With the identification of genes such as BRCA1 and BRCA2, which increase some women’s risk for breast and ovarian cancer, interest has intensified in finding the gene or genes, which predispose to prostate cancer.

As early as 1956, it was noted that prostate cancer patients reported a higher frequency of disease in their families than in control patients. The first segregation analysis was reported by Carter, Walsh and others from Johns Hopkins University in 1992. Their study of 691 families suggested that a gene with a dominant effect did indeed exist in a small percentage of families. Other studies from Sweden in 1997 and the Mayo clinic in 1998 supported the same type of inheritance. Several gene locations have been reported, including several different sites on chromosome 1, a site on the X chromosome, and chromosome 20. Efforts to isolate the actual genes at those locations are underway by many research groups nationally and internationally.

Recently, a group from Utah reported the cloning of a gene on chromosome 17 named HPC2/ELAC2. This gene is a member of a gene family, which appears to be highly conserved through evolution, although its exact function is not yet understood. While only a few families among those studied had a mutation in this gene, a second study from the University of Pennsylvania evaluated whether variations in this gene are associated with prostate cancer in individuals without a strong family history of the disease. They estimated that particular variants of this gene account for perhaps 5% of prostate cancer in the group of men that they studied. The HPC2/ELAC2 gene variants need further study to determine the contribution of these variants to prostate cancer in the general population.

The search for the actual prostate cancer genes has been slowed by the fact that prostate cancer is a common disease, and the same family may have members who have prostate cancer due to the inherited predisposing gene, and others who have the sporadic, more common, non-inherited form. Furthermore, inherited forms of prostate cancer do not appear different from the sporadic forms when the tissue is examined under the microscope. This inability to distinguish between inherited and sporadic forms makes it harder to identify the best individuals for intensive study.

Prostate cancer has also been associated with common variants in genes, which are involved in steroid hormone metabolism, such as the androgen receptor gene, SRD5A2, CYP3A4, and also the vitamin D receptor gene. The level of contributions of variations in these genes to the development of prostate cancer in a specific individual is still under study. Even BRCA1 and BRCA2 have come under scrutiny, with some reports suggesting a three to seven fold increase in risk for prostate cancer for men from families in which a mutation in one of these genes has been identified.

Recent progress in mapping the human genome will be helpful in the search to identify genes, which increase a man’s personal risk for developing prostate cancer. Once such genes are identified, appropriate screening and treatment of individuals at highest risk will be easier to plan. MACGN is involved in several studies supported by the Cancer Genetics Network to identify genes, which predispose for prostate cancer. If you are interested in these studies, please contact MACGN at 1-877-880-6188 or at our website www.MACGN.org

Constance Griffin, MD