Recent studies suggest that hereditary prostate cancer is a complex disease involving multiple susceptibility genes and variable phenotypic expression. While conducting a genomewide search on 162 North American families with ≥ 3 members affected with prostate cancer (PRCA), we found evidence for linkage to chromosome 20q13 with two-point parametric LOD scores ≥ 1 at multiple sites, with the highest two-point LOD score of 2.69 for marker D20S196. The maximum multipoint NPL score for the entire data set was 3.02 (P = .002) at D20S887. On the basis of findings from previous reports, families were stratified by the presence (n = 116) or absence (n = 46) of male-to-male transmission, average age of diagnosis (≤ 66 years, n = 73; ≥ 66 years, n = 89), and number of affected individuals (≤ 5, n = 101; ≥ 5, n = 61) for further analysis. The strongest evidence of linkage was evident with the pedigrees having ≤ 5 family members affected with prostate cancer (multipoint NPL 3.22, P = .00079), a later average age of diagnosis (multipoint NPL 3.4.0, P = .0006), and no male-to-male transmission (multipoint NPL 3.94, P = .00007). The group of patients having all three of these characteristics (n = 19) had a multipoint NPL score of 3.69 (P = .0001). These results demonstrate evidence for a PRCA susceptibility locus in a subset of families that is distinct from the groups more likely to be linked to previously identified loci.
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