Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3.
We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10⁻⁸) and rs7579899 (P = 2.3 × 10⁻⁹), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 × 10⁻¹⁴). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 × 10⁻⁸). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, Maryland, USA.
Mark P
MP
Purdue
Mattias
M
Johansson
Diana
D
Zelenika
Jorge R
JR
Toro
Ghislaine
G
Scelo
Lee E
LE
Moore
Egor
E
Prokhortchouk
Xifeng
X
Wu
Lambertus A
LA
Kiemeney
Valerie
V
Gaborieau
Kevin B
KB
Jacobs
Wong-Ho
WH
Chow
David
D
Zaridze
Vsevolod
V
Matveev
Jan
J
Lubinski
Joanna
J
Trubicka
Neonila
N
Szeszenia-Dabrowska
Jolanta
J
Lissowska
Péter
P
Rudnai
Eleonora
E
Fabianova
Alexandru
A
Bucur
Vladimir
V
Bencko
Lenka
L
Foretova
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
Anush
A
Mukeria
Oxana
O
Shangina
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
Stephanie J
SJ
Weinstein
Jarmo
J
Virtamo
Lars
L
Vatten
Kristian
K
Hveem
Inger
I
Njølstad
Grethe S
GS
Tell
Camilla
C
Stoltenberg
Rajiv
R
Kumar
Kvetoslava
K
Koppova
Olivier
O
Cussenot
Simone
S
Benhamou
Egbert
E
Oosterwijk
Sita H
SH
Vermeulen
Katja K H
KK
Aben
Saskia L
SL
van der Marel
Yuanqing
Y
Ye
Christopher G
CG
Wood
Xia
X
Pu
Alexander M
AM
Mazur
Eugenia S
ES
Boulygina
Nikolai N
NN
Chekanov
Mario
M
Foglio
Doris
D
Lechner
Ivo
I
Gut
Simon
S
Heath
Hélène
H
Blanche
Amy
A
Hutchinson
Gilles
G
Thomas
Zhaoming
Z
Wang
Meredith
M
Yeager
Joseph F
JF
Fraumeni
Konstantin G
KG
Skryabin
James D
JD
McKay
Nathaniel
N
Rothman
Stephen J
SJ
Chanock
Mark
M
Lathrop
Paul
P
Brennan
D002292:Carcinoma, Renal Cell / Q000235:genetics*; D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors