The major focus of this study will be to collect families with (a) three or more prostatic cancer cases diagnosed at any age; or (b) two or more affected brothers diagnosed before the age of 65 years. Such families are candidates for carrying an inherited susceptibility predisposing to prostatic and possibly other malignancies. The families will be collected through major clinical urology centres through Europe. This bank of material, both DNA and RNA, will then be available for molecular genetic studies to identify genes predisposing to prostate cancer. The project will initially use genetic linkage analysis to identify genes which contribute to the risk of prostate cancer and to assess the importance of this gene/these genes to familial prostate cancer. DNA markers which are usually based on microsatellite repeats and which are known to have high degrees of polymorphism are typed within the families and tested for co-segregation with the putative prostate cancer susceptibility gene. Evidence for co-segregation is assessed statistically. The analysis will focus on a variety of candidate genes which are known to play a role in either prostate development or in other cancer susceptibility syndromes such as those for the breast cancer syndromes, BRCA1 and BRCA2. Only in the event that none of these turn out to be important would a genome-wide mapping search be initiated. When a gene or more probably a genetic region is identified as being important, we will assess the importance of this region to familial prostate cancer.
The other approach will be to examine the importance of genes thought to modify the risk of prostate cancer using a case-control approach. We will collaborate with ongoing studies which are investigating environmental causes of prostate cancer to examine the role of gene-environment interactions in determining prostate cancer susceptibility.