Evidence for a prostate cancer-susceptibility locus on chromosome 20.
Recent studies suggest that hereditary prostate cancer is a complex disease involving multiple susceptibility genes and variable phenotypic expression. While conducting a genomewide search on 162 North American families with > or =3 members affected with prostate cancer (PRCA), we found evidence for linkage to chromosome 20q13 with two-point parametric LOD scores >1 at multiple sites, with the highest two-point LOD score of 2.69 for marker D20S196. The maximum multipoint NPL score for the entire data set was 3.02 (P=.002) at D20S887. On the basis of findings from previous reports, families were stratified by the presence (n=116) or absence (n=46) of male-to-male transmission, average age of diagnosis (<66 years, n=73; > or =66 years, n=89), and number of affected individuals (<5, n=101; > or =5, n=61) for further analysis. The strongest evidence of linkage was evident with the pedigrees having <5 family members affected with prostate cancer (multipoint NPL 3.22, P=.00079), a later average age of diagnosis (multipoint NPL 3.40, P=.0006), and no male-to-male transmission (multipoint NPL 3.94, P=.00007). The group of patients having all three of these characteristics (n=19) had a multipoint NPL score of 3.69 (P=.0001). These results demonstrate evidence for a PRCA susceptibility locus in a subset of families that is distinct from the groups more likely to be linked to previously identified loci.
Berry
R
R
Department of Laboratory Medicine and Pathology, Mayo Clinic/Foundation, Rochester, MN 55905, USA.
Schroeder
J J
JJ
French
A J
AJ
McDonnell
S K
SK
Peterson
B J
BJ
Cunningham
J M
JM
Thibodeau
S N
SN
Schaid
D J
DJ
D017668:Age of Onset; D000368:Aged; D000483:Alleles; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D018740:Genetic Heterogeneity; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012984:Software; D018709:Statistics, Nonparametric
D005819:Genetic Markers