Refining the prostate cancer genetic association within the JAZF1 gene on chromosome 7p15.2.
BACKGROUND
Genome-wide association studies have identified multiple genetic variants associated with susceptibility to prostate cancer (PrCa). In the two-stage Cancer Genetic Markers of Susceptibility prostate cancer scan, a single-nucleotide polymorphism (SNP), rs10486567, located within intron 2 of JAZF1 gene on chromosome 7p15.2, showed a promising association with PrCa overall (P=2.14x10(-6)), with a suggestion of stronger association with aggressive disease (P=1.2x10(-7)).


METHODS
In the third stage of genome-wide association studies, we genotyped 106 JAZF1 SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry.


RESULTS
The strongest association was observed with the initial marker rs10486567, which now achieves genome-wide significance [P=7.79x10(-11); ORHET, 1.19 (95% confidence interval, 1.12-1.27); ORHOM, 1.37 (95% confidence interval, 1.20-1.56)]. We did not confirm a previous suggestion of a stronger association of rs10486567 with aggressive disease (P=1.60x10(-4) for aggressive cancer, n=4,597; P=3.25x10(-8) for nonaggressive cancer, n=4,514). Based on a multilocus model with adjustment for rs10486567, no additional independent signals were observed at chromosome 7p15.2. There was no association between PrCa risk and SNPs in JAZF1 previously associated with height (rs849140; P=0.587), body stature (rs849141, tagged by rs849136; P=0.171), and risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142; P=0.657).


CONCLUSIONS
rs10486567 remains the most significant marker for PrCa risk within JAZF1 in individuals of European ancestry.


CONCLUSIONS
Future studies should identify all variants in high linkage disequilibrium with rs10486567 and evaluate their functional significance for PrCa.
Prokunina-Olsson
Ludmila
L
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 8717 Grovemont Circle, Bethesda, MD 20892-4605, USA. prokuninal@mail.nih.gov
Fu
Yi-Ping
YP
Tang
Wei
W
Jacobs
Kevin B
KB
Hayes
Richard B
RB
Kraft
Peter
P
Berndt
Sonja I
SI
Wacholder
Sholom
S
Yu
Kai
K
Hutchinson
Amy
A
Spencer Feigelson
Heather
H
Thun
Michael J
MJ
Diver
W Ryan
WR
Albanes
Demetrius
D
Virtamo
Jarmo
J
Weinstein
Stephanie
S
Schumacher
Fredrick R
FR
Cancel-Tassin
Geraldine
G
Cussenot
Olivier
O
Valeri
Antoine
A
Andriole
Gerald L
GL
Crawford
E David
ED
Haiman
Christopher A
CA
Henderson
Brian E
BE
Kolonel
Laurence
L
Le Marchand
Loic
L
Siddiq
Afshan
A
Riboli
Elio
E
Travis
Ruth
R
Kaaks
Rudolf
R
Isaacs
William B
WB
Isaacs
Sarah D
SD
Grönberg
Henrik
H
Wiklund
Fredrik
F
Xu
Jianfeng
J
Vatten
Lars J
LJ
Hveem
Kristian
K
Kumle
Merethe
M
Tucker
Margaret
M
Hoover
Robert N
RN
Fraumeni
Joseph F
JF
Hunter
David J
DJ
Thomas
Gilles
G
Chatterjee
Nilanjan
N
Chanock
Stephen J
SJ
Yeager
Meredith
M
D016022:Case-Control Studies; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C430460:JAZF1 protein, human; D009363:Neoplasm Proteins
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