Results of a genome-wide linkage analysis in prostate cancer families ascertained through the ACTANE consortium.
BACKGROUND
The aggregation of prostate cancer within families suggests a major inherited component to the disease. Genetic linkage studies have identified several chromosomal regions that may contain prostate cancer susceptibility loci, but none has been definitively implicated.


METHODS
We performed a genome-wide linkage search based on 64 families, 63 with at least 3 cases of prostate cancer, ascertained in five countries. The majority of cases from these centers presented with clinically detected disease. Four hundred and one polymorphic markers were typed in 268 individuals. Multipoint heterogeneity analysis was conducted under three models of susceptibility; non-parametric analyses were also performed.


RESULTS
Some weak evidence of linkage, under at least one of the genetic models, was observed to markers on chromosomes 2 (heterogeneity LOD (HLOD) = 1.15, P = 0.021), 3 (HLOD = 1.25, P = 0.016), 4 (HLOD = 1.28, P = 0.015), 5 (HLOD = 1.20, P = 0.019), 6 (HLOD = 1.41, P = 0.011), and 11 (HLOD = 1.24, P = 0.018), and in two regions on chromosome 18 (HLOD = 1.40, P = 0.011 and HLOD = 1.34, P = 0.013). There were no HLOD scores greater than 1.5 under any model, and no locus would be predicted to explain more than half of the genetic effect. No evidence in favor of linkage to previously suggested regions on chromosomes 1, 8, 17, 20, or X was found.


CONCLUSIONS
Genetic susceptibility to prostate cancer is likely to be controlled by many loci, with no single gene explaining a large fraction of the familial risk. Pooling of results from all available genome scans is likely to be required to obtain definitive linkage results.
Steve
S
Edwards
Julia
J
Meitz
Ros
R
Eles
Chris
C
Evans
Doug
D
Easton
John
J
Hopper
Graham
G
Giles
William D
WD
Foulkes
Steven
S
Narod
Jacques
J
Simard
Mike
M
Badzioch
Lovise
L
Mahle
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005190:Family; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics*; D017422:Sequence Analysis, DNA
D004273:DNA, Neoplasm