Purpose: Hereditary prostate cancer is an etiologically heterogeneous disea
se with six susceptibility loci mapped to date. We aimed to describe a coll
ection of high-risk prostate cancer families and assess linkage to multiple
markers at four loci: HPC1 (1q24-25), PCaP (1q42.2-43), HPCX (Xq27-28), an
d CAPB (1p36).
Experimental Design: Medical record data on 505 affected men in 149 multipl
y-affected prostate cancer families were reviewed, and correlations of clin
ical traits within each family were calculated. Logarithm of odds (LOD) sco
re and nonparametric (NPL) linkage analyses were performed;; white families
were stratified by age of diagnosis, grade and stage of disease, and evide
nce of linkage to the other loci to increase genetic homogeneity.
Results: Age at diagnosis was the most correlated clinical trait within fam
ilies. A maximum NPL score of 2.61 (P = 0.007) appeared to confirm HPC1 lin
kage for families that had a prevalence of high-grade or advanced-stage pro
state cancer and which were not likely to be linked to PCaP, HPCX, or CAPB.
Because the NPL scores improved when families more likely to be linked to
the other loci were excluded, HPC1 may act independently of the other loci.
The relationship of HPC1 and aggressive disease was strongest in families
with median age at diagnosis greater than or equal to 65 years (NPL, 3.48;
P = 0.0008).
Conclusions: The current results suggest that HPC1 linkage may be most comm
on among families with more severe prostate cancer. Stratification by clini
cal characteristics may be a useful tool in prostate cancer linkage analyse
s and may increase our understanding of hereditary prostate cancer.