Evidence for a Prostate Cancer-Susceptibility Locus on Chromosome 20

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 ( n =73; ⩾66 years, n =89), and number of affected individuals ( n =101; ⩾5, n =61) for further analysis. The strongest evidence of linkage was evident with the pedigrees having P =.00079), a later average age of diagnosis (multipoint NPL 3.40, 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.