Genome-wide linkage scan for prostate cancer aggressiveness loci using families from the University of Michigan Prostate Cancer Genetics Project.
BACKGROUND
Prostate cancer (PC) is a complex disease that displays variable disease outcome, ranging from a relatively indolent disease to forms that result in death from the disease. One measure of disease severity is the Gleason score. Using the Gleason score as a measure of tumor aggressiveness, several independent genome scans have reported evidence of linkage. As of yet, however, no genes have been implicated.


METHODS
We report an independent genome scan using the Gleason score as a quantitative trait. We genotyped 405 highly polymorphic microsatellite markers in 175 brother pairs from 103 families.


RESULTS
Our strongest evidence of linkage is to 6q23 at 137 cM (D6S292, P = 0.0009). Other interesting regions (P < 0.005) were on chromosome 1p13-q21 and on chromosome 5p13-q11.


CONCLUSIONS
Our results provide further evidence that tumor aggressiveness has a genetic component, and that this genetic component may be influenced by several independent genes.
Slager
Susan L
SL
Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. slager@mayo.edu
Zarfas
Katherine E
KE
Brown
W Mark
WM
Lange
Ethan M
EM
McDonnell
Shannon K
SK
Wojno
Kirk J
KJ
Cooney
Kathleen A
KA
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D004261:DNA Replication; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics*; D010375:Pedigree; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D012720:Severity of Illness Index; D044465:White People / Q000235:genetics