Two-locus genome-wide linkage scan for prostate cancer susceptibility genes with an interaction effect.
Prostate cancer represents a significant worldwide public health burden. Epidemiological and genetic epidemiological studies have consistently provided data supporting the existence of inherited prostate cancer susceptibility genes. Segregation analyses of prostate cancer suggest that a multigene model may best explain familial clustering of this disease. Therefore, modeling gene-gene interactions in linkage analysis may improve the power to detect chromosomal regions harboring these disease susceptibility genes. In this study, we systematically screened for prostate cancer linkage by modeling two-locus gene-gene interactions for all possible pairs of loci across the genome in 426 prostate cancer families from Johns Hopkins Hospital, University of Michigan, University of Umeå, and University of Tampere. We found suggestive evidence for an epistatic interaction for six sets of loci (target chromosome-wide/reference marker-specific P< or =0.0001). Evidence for these interactions was found in two independent subsets from within the 426 families. While the validity of these results requires confirmation from independent studies and the identification of the specific genes underlying this linkage evidence, our approach of systematically assessing gene-gene interactions across the entire genome represents a promising alternative approach for gene identification for prostate cancer.
Chang
Bao-Li
BL
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Lange
Ethan M
EM
Dimitrov
Latchezar
L
Valis
Christopher J
CJ
Gillanders
Elizabeth M
EM
Lange
Leslie A
LA
Wiley
Kathleen E
KE
Isaacs
Sarah D
SD
Wiklund
Fredrik
F
Baffoe-Bonnie
Agnes
A
Langefeld
Carl D
CD
Zheng
S Lilly
SL
Matikainen
Mika P
MP
Ikonen
Tarja
T
Fredriksson
Henna
H
Tammela
Teuvo
T
Walsh
Patrick C
PC
Bailey-Wilson
Joan E
JE
Schleutker
Johanna
J
Gronberg
Henrik
H
Cooney
Kathleen A
KA
Isaacs
William B
WB
Suh
Edward
E
Trent
Jeffrey M
JM
Xu
Jianfeng
J
D000368:Aged; D002277:Carcinoma / Q000235:genetics*; D005190:Family; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*
D005819:Genetic Markers