Genome‐wide linkage analysis for aggressive prostate cancer in Utah high‐risk pedigrees

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Abstract
BACKGROUND It has been proposed that studying alternative phenotypes, such as tumor aggressiveness, may be a solution for overcoming the apparent heterogeneity that has hindered the identification of prostate cancer (PC) genes. We present the results of a genome‐scan for predisposition to aggressive PC using the Utah high‐risk pedigree resource. METHODS We identified 259 subjects with aggressive PC in 57 extended and nuclear families. Parametric and non‐parametric multipoint linkage statistics were calculated for a genome‐wide set of 401 microsatellite markers using the MCLINK software package. Stratification analyses by the number of affected subjects per pedigree ( 0.58). The subset of pedigrees with earlier age at onset demonstrated nominal linkage evidence on chromosomes 3q (HLOD = 1.79), 8q (HLOD = 1.67), and 20q (HLOD=1.82). The late‐onset subset showed suggestive linkage on chromosome 6p (HLOD = 2.37) and the subset of pedigrees with fewer than five affected subjects showed suggestive linkage on chromosome 10p (HLOD = 1.99). CONCLUSIONS Linkage evidence observed on chromosomes 6p, 8q, and 20q support previously reported PC aggressiveness loci. While these results are encouraging, further research is necessary to identify the gene or genes responsible for PC aggressiveness and surmount the overarching problem of PC heterogeneity. Prostate 67: 605–613, 2007.