Genome-wide scan for prostate cancer susceptibility genes using families from the University of Michigan prostate cancer genetics project finds evidence for linkage on chromosome 17 near BRCA1.
BACKGROUND
Previous linkage studies have suggested prostate cancer susceptibility genes located on chromosomes 1, 20, and X. Several putative prostate cancer candidate genes have also been identified including RNASEL, MSR1, and ELAC2. Presently, these linkage regions and candidate genes appear to explain only a small proportion of hereditary prostate cancer cases suggesting the need for additional whole genome analyses.


METHODS
A genome-wide mode-of-inheritance-free linkage scan, using 405 genetic markers, was conducted on 175 pedigrees, the majority containing three or more affected individuals diagnosed with prostate cancer. Stratified linkage analyses were performed based on previously established criteria.


RESULTS
Results based on the entire set of 175 pedigrees showed strong suggestive evidence for linkage on chromosome 17q (LOD = 2.36), with strongest evidence coming from the subset of pedigrees with four or more affected individuals (LOD = 3.27). Race specific analyses revealed strong suggestive evidence for linkage in our African-American pedigrees on chromosome 22q (LOD = 2.35).


CONCLUSIONS
Genome-wide analysis of a large set of prostate cancer families indicates new areas of the genome that may harbor prostate cancer susceptibility genes. Specifically, our linkage results suggest that there is a prostate cancer susceptibility gene on chromosome 17 that is independent of ELAC2. Further research including combined analyses of independent genome-wide scan data may clarify the most important regions for future investigation.
Lange
Ethan M
EM
Department of Public Health Sciences, Section on Biostatistics, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157-1063, USA. elange@wfubmc.edu
Gillanders
Elizabeth M
EM
Davis
Cralen C
CC
Brown
W Mark
WM
Campbell
Joel K
JK
Jones
MaryPat
M
Gildea
Derek
D
Riedesel
Erica
E
Albertus
Julie
J
Freas-Lutz
Diana
D
Markey
Carol
C
Giri
Veda
V
Dimmer
Jennifer Beebe
JB
Montie
James E
JE
Trent
Jeffrey M
JM
Cooney
Kathleen A
KA
D017668:Age of Onset; D000368:Aged; D044383:Black People; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005190:Family; D019398:Genes, BRCA1; 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; D044465:White People; D001741:Black or African American
D004273:DNA, Neoplasm