A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23.
Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r(2) = 0.64, D ' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10(-10) and P = 6.07 × 10(-9), respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.
Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. xwu@mdanderson.org
Xifeng
X
Wu
Ghislaine
G
Scelo
Mark P
MP
Purdue
Nathaniel
N
Rothman
Mattias
M
Johansson
Yuanqing
Y
Ye
Zhaoming
Z
Wang
Diana
D
Zelenika
Lee E
LE
Moore
Christopher G
CG
Wood
Egor
E
Prokhortchouk
Valerie
V
Gaborieau
Kevin B
KB
Jacobs
Wong-Ho
WH
Chow
Jorge R
JR
Toro
David
D
Zaridze
Jie
J
Lin
Jan
J
Lubinski
Joanna
J
Trubicka
Neonilia
N
Szeszenia-Dabrowska
Jolanta
J
Lissowska
Peter
P
Rudnai
Eleonora
E
Fabianova
Dana
D
Mates
Viorel
V
Jinga
Vladimir
V
Bencko
Alena
A
Slamova
Ivana
I
Holcatova
Marie
M
Navratilova
Vladimir
V
Janout
Paolo
P
Boffetta
Joanne S
JS
Colt
Faith G
FG
Davis
Kendra L
KL
Schwartz
Rosamonde E
RE
Banks
Peter J
PJ
Selby
Patricia
P
Harnden
Christine D
CD
Berg
Ann W
AW
Hsing
Robert L
RL
Grubb
Heiner
H
Boeing
Paolo
P
Vineis
Françoise
F
Clavel-Chapelon
Domenico
D
Palli
Rosario
R
Tumino
Vittorio
V
Krogh
Salvatore
S
Panico
Eric J
EJ
Duell
José Ramón
JR
Quirós
Maria-José
MJ
Sanchez
Carmen
C
Navarro
Eva
E
Ardanaz
Miren
M
Dorronsoro
Kay-Tee
KT
Khaw
Naomi E
NE
Allen
H Bas
HB
Bueno-de-Mesquita
Petra H M
PH
Peeters
Dimitrios
D
Trichopoulos
Jakob
J
Linseisen
Börje
B
Ljungberg
Kim
K
Overvad
Anne
A
Tjønneland
Isabelle
I
Romieu
Elio
E
Riboli
Victoria L
VL
Stevens
Michael J
MJ
Thun
W Ryan
WR
Diver
Susan M
SM
Gapstur
Paul D
PD
Pharoah
Douglas F
DF
Easton
Demetrius
D
Albanes
Jarmo
J
Virtamo
Lars
L
Vatten
Kristian
K
Hveem
Tony
T
Fletcher
Kvetoslava
K
Koppova
Olivier
O
Cussenot
Geraldine
G
Cancel-Tassin
Simone
S
Benhamou
Michelle A
MA
Hildebrandt
Xia
X
Pu
Mario
M
Foglio
Doris
D
Lechner
Amy
A
Hutchinson
Meredith
M
Yeager
Joseph F
JF
Fraumeni
Mark
M
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Konstantin G
KG
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James D
JD
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Jian
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Stephen J
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Chanock
D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*