Evidence for a prostate cancer-susceptibillty 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 greater than or equal to 3 members affected with prostate cancer (PRCA), we found evidence for linkage to chromosome 20q13 with two-point parametric L OD scores >1 at multiple sites, with the highest two-point LOD score of 2.6 9 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 r eports, families were stratified by the presence (n = 116) or absence (n = 46) of male-to-male transmission, average age of diagnosis (<66 pears, n = 73; greater than or equal to 66 years, n = 89), and number of affected indi viduals (<5, n = 101; greater than or equal to 5, n = 61) for further analy sis. The strongest evidence of linkage was evident with the pedigrees havin g <5 family members affected with prostate cancer (multipoint NPL 3.22, P=. 00079), a later average age of diagnosis (multipoint NPL 3.40, P=.0006), an d 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 multip oint NPL score of 3.63 (P =.0001). These results demonstrate evidence for a PRCA susceptibility locus in a subset of families that is distinct from th e groups more likely to be linked to previously identified loci.