In Swedish families with hereditary prostate cancer, linkage to the HPC1 locus on chromosome 1q24-25 is restricted to families with early-onset prostate cancer

Prostate cancer clusters in some families, and an estimated 5%-10% of all c ases are estimated to result from inheritance of prostate cancer-susceptibi lity genes. We previously reported evidence of linkage to the 1q24-25 regio n (HPC1) in 91 North American and Swedish families each with multiple cases of prostate cancer (Smith et al. 1996). In the present report we analyze 4 0 (12 original and 28 newly identified) Swedish families with hereditary pr ostate cancer (HPC) that, on the basis of 40 markers spanning a 25-cM inter val within 1q24-25, have evidence of linkage. In the complete set of famili es, a maximum two-point LOD score of 1.10 was observed at D1S413 (at a reco mbination fraction [theta] of .1), with a maximum NPL (nonparametric linkag e) Z score of 1.64 at D1S202 (P = .05). The evidence of linkage to this reg ion originated almost exclusively from the subset of 12 early-onset (age <6 5 years) families, which yielded a maximum LOD score of 2.38 at D1S413 (the ta = 0) and an NPL Z score of 1.95 at D1S422 (P = .03). Estimates from hete rogeneity tests suggest that, within Sweden, as many as 50% of early-onset families had evidence of linkage to the HPC1 region. These results are cons istent with the hypothesis of linkage to HPC1 in a subset of families with prostate cancer, particularly those with an early age at diagnosis.