Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36

Combining data from a genomic screen in 70 families with a high risk for pr ostate cancer (PC) with data from candidate-region mapping in these familie s and an additional 71 families, we have localized a potential hereditary P C-susceptibility locus to chromosome 1p36. Because an excess of cases of pr imary brain cancer (BC) have been observed in some studies of families with a high risk for PC, and because loss of heterozygosity at 1p36 is frequent ly observed in BC, we further evaluated 12 families with both a history of PC and a blood relative with primary BC. The overall LOD score in these 12 families was 3.22 at a recombination fraction (theta) of .06, with marker D 1S507. On the basis of an a priori hypothesis, this group was stratified by age at diagnosis of PC. In the younger age group (mean age at diagnosis <6 6 years), a maximum two-point LOD score of 3.65 at theta = .0 was observed, with D1S407. This linkage was rejected in both early- and late-onset famil ies without a history of BC (LOD scores -7.12 and -6.03, respectively, at t heta = .0). After exclusion of 3 of the 12 families that had better evidenc e of linkage to previously described PC-susceptibility loci, linkage to the 1p36 region was suggested by a two-point LOD score of 4.74 at theta = .0, with marker D1S407. We conclude that a significant proportion of these fami lies with both a high risk for PC and a family member with BC show linkage to the 1p36 region.