Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36.
Combining data from a genomic screen in 70 families with a high risk for prostate cancer (PC) with data from candidate-region mapping in these families and an additional 71 families, we have localized a potential hereditary PC-susceptibility locus to chromosome 1p36. Because an excess of cases of primary brain cancer (BC) have been observed in some studies of families with a high risk for PC, and because loss of heterozygosity at 1p36 is frequently observed in BC, we further evaluated 12 families with both a history of PC and a blood relative with primary BC. The overall LOD score in these 12 families was 3.22 at a recombination fraction (theta) of .06, with marker D1S507. On the basis of an a priori hypothesis, this group was stratified by age at diagnosis of PC. In the younger age group (mean age at diagnosis <66 years), a maximum two-point LOD score of 3.65 at straight theta = .0 was observed, with D1S407. This linkage was rejected in both early- and late-onset families without a history of BC (LOD scores -7.12 and -6.03, respectively, at straight theta = .0). After exclusion of 3 of the 12 families that had better evidence of linkage to previously described PC-susceptibility loci, linkage to the 1p36 region was suggested by a two-point LOD score of 4.74 at straight theta = .0, with marker D1S407. We conclude that a significant proportion of these families with both a high risk for PC and a family member with BC show linkage to the 1p36 region.
Division of Clinical Research, Fred Hutchinson Cancer Research Center, D2-190, Seattle, WA 98109-1024, USA.
M
M
Gibbs
J L
JL
Stanford
R A
RA
McIndoe
G P
GP
Jarvik
S
S
Kolb
E L
EL
Goode
L
L
Chakrabarti
E F
EF
Schuster
V A
VA
Buckley
E L
EL
Miller
S
S
Brandzel
S
S
Li
L
L
Hood
E A
EA
Ostrander
D000368:Aged; D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008126:Lod Score; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D019683:Penetrance; D011471:Prostatic Neoplasms / Q000235:genetics*
D005819:Genetic Markers