Genomic scan of 254 hereditary prostate cancer families.
Hereditary prostate cancer (HPC) is a genetically heterogeneous disease, complicating efforts to map and clone susceptibility loci. We have used stratification of a large dataset of 254 HPC families in an effort to improve power to detect HPC loci and to understand what types of family features may improve locus identification. The strongest result is that of a dominant locus at 6p22.3 (heterogeneity LOD (HLOD) = 2.51), the evidence for which is increased by consideration of the age of PC onset (HLOD = 3.43 in 214 families with median age-of-onset 56-72 years) and co-occurrence of primary brain cancer (HLOD = 2.34 in 21 families) in the families. Additional regions for which we observe modest evidence for linkage include chromosome 7q and 17p. Only weak evidence of several previously implicated HPC regions is detected. These analyses support the existence of multiple HPC loci, whose presence may be best identified by analyses of large, including pooled, datasets which consider locus heterogeneity.
Institute for Systems Biology, Seattle, Washington, USA.
Marta
M
Janer
Danielle M
DM
Friedrichsen
Janet L
JL
Stanford
Michael D
MD
Badzioch
Suzanne
S
Kolb
Kerry
K
Deutsch
Mette A
MA
Peters
Ellen L
EL
Goode
Russ
R
Welti
Hawkins B
HB
DeFrance
Lori
L
Iwasaki
Sarah
S
Li
Leroy
L
Hood
Elaine A
EA
Ostrander
Gail P
GP
Jarvik
D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005190:Family; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm; D005819:Genetic Markers