Clinical characteristics of prostate cancer in an analysis of linkage to four putative susceptibility loci

Citation
El. Goode et al., Clinical characteristics of prostate cancer in an analysis of linkage to four putative susceptibility loci, CLIN CANC R, 7(9), 2001, pp. 2739-2749
Citations number
100
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
7
Issue
9
Year of publication
2001
Pages
2739 - 2749
Database
ISI
SICI code
1078-0432(200109)7:9<2739:CCOPCI>2.0.ZU;2-N
Abstract
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.