Analysis of chromosome 1q42.2-43 in 152 families with high risk of prostate cancer.
One hundred fifty-two families with prostate cancer were analyzed for linkage to markers spanning a 20-cM region of 1q42.2-43, the location of a putative prostate cancer-susceptibility locus (PCAP). No significant evidence for linkage was found, by use of both parametric and nonparametric tests, in our total data set, which included 522 genotyped affected men. Rejection of linkage may reflect locus heterogeneity or the confounding effects of sporadic disease in older-onset cases; therefore, pedigrees were stratified into homogeneous subsets based on mean age at diagnosis of prostate cancer and number of affected men. Analyses of these subsets also detected no significant evidence for linkage, although LOD scores were positive at higher recombination fractions, which is consistent with the presence of a small proportion of families with linkage. The most suggestive evidence of linkage was in families with at least five affected men (nonparametric linkage score of 1.2; P=.1). If heterogeneity is assumed, an estimated 4%-9% of these 152 families may show linkage in this region. We conclude that the putative PCAP locus does not account for a large proportion of these families with prostate cancer, although the linkage of a small subset is compatible with these data.
Gibbs
M
M
Division of Clinical Research, D2-190, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Chakrabarti
L
L
Stanford
J L
JL
Goode
E L
EL
Kolb
S
S
Schuster
E F
EF
Buckley
V A
VA
Shook
M
M
Hood
L
L
Jarvik
G P
GP
Ostrander
E A
EA
D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D018709:Statistics, Nonparametric