Genome-wide scan for prostate cancer susceptibility genes in the Johns Hopkins hereditary prostate cancer families.
BACKGROUND
Although the subject of intensive study, the genetic influences responsible for familial clustering of prostate cancer remain largely unidentified. Genome-wide scans for linkage in prostate cancer families can be used to systematically search for genes capable of affecting risk for the disease.


METHODS
All available family members from 188 families, each having at least three first-degree relatives affected with prostate cancer, were genotyped at 406 markers distributed across the genome at average intervals of less than 10 cM. Genotype data was analyzed using primarily a non-parametric, multipoint approach, although parametric analyses were performed as well.


RESULTS
The strongest evidence for linkage was observed at D4S1615, at 4q21 (LOD of 2.8, P = 0.0002). Two other regions had LOD scores over 2.0: at 9q34 (marker D9S1826, LOD = 2.17, P = 0.0008) and at 2q23 (marker D2S151, LOD = 2.03, P = 0.001). An additional 12 regions had LOD scores over 1.0, including markers at 1q24-25 and 7q22 having scores >1.6. Stratifying the linkage results by age of diagnosis indicated that the linkages to chromosomes 2 and 4 were strongest in families with early and late ages of diagnosis, respectively.


CONCLUSIONS
Our data implicate several new loci as harboring prostate cancer susceptibility genes, and provide confirmatory evidence of linkage at several loci identified previously in other genome-wide scans, including the three regions (4q21, 9q34, and 2q23) with strongest evidence for prostate cancer linkage. These data also emphasize the need to combine linkage data from large numbers of prostate cancer families in efforts to effectively address the extensive heterogeneity that characterizes genetic aspects of this disease.
Xu
Jianfeng
J
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Gillanders
Elizabeth M
EM
Isaacs
Sarah D
SD
Chang
Bao-Li
BL
Wiley
Kathy E
KE
Zheng
S Lilly
SL
Jones
MaryPat
M
Gildea
Derek
D
Riedesel
Erica
E
Albertus
Julie
J
Freas-Lutz
Diana
D
Markey
Carol
C
Meyers
Deborah A
DA
Walsh
Patrick C
PC
Trent
Jeffrey M
JM
Isaacs
William B
WB
D000368:Aged; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005190:Family; 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; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics*; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric
D004273:DNA, Neoplasm; D005819:Genetic Markers