Genome-wide linkage scan for prostate cancer aggressiveness loci using families from the University of Michigan prostate cancer genetics project

BACKGROUND. Prostate cancer (PC) is a complex disease that displays variable disease outcome, ranging from a relatively indolent disease to forms that result in death from the disease. One measure of disease severity is the Gleason score. Using the Gleason score as a measure of tumor aggressiveness, several independent genome scans have reported evidence of linkage. As of yet, however, no genes have been implicated. METHODS. We report an independent genome scan using the Gleason score as a quantitative trait. We genotyped 405 highly polymorphic microsatellite markers in 175 brother pairs from 103 families. RESULTS. Our strongest evidence of linkage is to 6q23 at 137 cM (D6S292, P = 0.0009). Other interesting regions (P < 0.005) were on chromosome 1p13-q21 and on chromosome 5p13-q11. CONCLUSIONS. Our results provide further evidence that tumor aggressiveness has a genetic component, and that this genetic component may be influenced by several independent genes.