title: Clinical characteristics of prostate cancer in an analysis of linkage to four putative susceptibility loci.
abstract: OBJECTIVE
  Hereditary prostate cancer is an etiologically heterogeneous disease with six susceptibility loci mapped to date. We aimed to describe a collection 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), and CAPB (1p36).
  
  
  METHODS
  Medical record data on 505 affected men in 149 multiply-affected prostate cancer families were reviewed, and correlations of clinical traits within each family were calculated. Logarithm of odds (LOD) score and nonparametric (NPL) linkage analyses were performed; white families were stratified by age of diagnosis, grade and stage of disease, and evidence of linkage to the other loci to increase genetic homogeneity.
  
  
  RESULTS
  Age at diagnosis was the most correlated clinical trait within families. A maximum NPL score of 2.61 (P = 0.007) appeared to confirm HPC1 linkage for families that had a prevalence of high-grade or advanced-stage prostate 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 > or =65 years (NPL, 3.48; P = 0.0008).
  
  
  CONCLUSIONS
  The current results suggest that HPC1 linkage may be most common among families with more severe prostate cancer. Stratification by clinical characteristics may be a useful tool in prostate cancer linkage analyses and may increase our understanding of hereditary prostate cancer.
authors.affiliation: Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, 98195-7236, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Goode
authors.forename: J L
authors.initials: JL
authors.lastname: Stanford
authors.forename: M A
authors.initials: MA
authors.lastname: Peters
authors.forename: M
authors.initials: M
authors.lastname: Janer
authors.forename: M
authors.initials: M
authors.lastname: Gibbs
authors.forename: S
authors.initials: S
authors.lastname: Kolb
authors.forename: M D
authors.initials: MD
authors.lastname: Badzioch
authors.forename: L
authors.initials: L
authors.lastname: Hood
authors.forename: E A
authors.initials: EA
authors.lastname: Ostrander
authors.forename: G P
authors.initials: GP
authors.lastname: Jarvik
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005192:Family Health; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D005819:Genetic Markers