Hereditary Prostate Cancer: Clinical Aspects

Abstract

We review the current epidemiological and genetic knowledge regarding hereditary prostate cancer, and outline its clinical implications. Published articles on hereditary prostate cancer were identified using the MEDLINE data base. A risk of prostate cancer, particularly early onset disease, is strongly affected by family history (number of relatives with prostate cancer and their age at diagnosis). A family history of prostate cancer increases the positive predictive value of prostate specific antigen testing and, hence, heredity should always be assessed when deciding whether to perform biopsies in a man with a prostate specific antigen level of 3 to 10 ng./ml. Epidemiological studies indicate that dominantly inherited susceptibility genes with high penetrance cause 5% to 10% of all prostate cancer cases, and as much as 30% to 40% of early onset disease. More than a half dozen chromosome loci that may comprise such genes have been mapped, but as of May 2002 no prostate cancer susceptibility gene of major importance had been cloned. Most likely, environmental factors and comparatively common variants of several other genes affect prostate cancer risk in families with or without multiple cases of the disease. On average, hereditary prostate cancer is diagnosed 6 to 7 years earlier than sporadic prostate cancer, but does not otherwise differ clinically from the sporadic form. As a consequence of the earlier onset, a greater proportion of men with hereditary prostate cancer die of the disease than those with nonhereditary prostate cancer. At present, the only clinically applicable measure to reduce prostate cancer mortality in families with hereditary disease is screening, with the aim of diagnosing the disease when it is still in a curable stage. Hereditary susceptibility is now considered the strongest risk factor for prostate cancer and has profound clinical importance. The genetic mechanism behind such susceptibility has turned out to be more complex than initially thought, and will probably not be completely understood for many years to come.