Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls.
Recent genome-wide association studies (GWASs) have identified common genetic variants at 5p15.33, 6p21-6p22 and 15q25.1 associated with lung cancer risk. Several other genetic regions including variants of CHEK2 (22q12), TP53BP1 (15q15) and RAD52 (12p13) have been demonstrated to influence lung cancer risk in candidate- or pathway-based analyses. To identify novel risk variants for lung cancer, we performed a meta-analysis of 16 GWASs, totaling 14 900 cases and 29 485 controls of European descent. Our data provided increased support for previously identified risk loci at 5p15 (P = 7.2 × 10(-16)), 6p21 (P = 2.3 × 10(-14)) and 15q25 (P = 2.2 × 10(-63)). Furthermore, we demonstrated histology-specific effects for 5p15, 6p21 and 12p13 loci but not for the 15q25 region. Subgroup analysis also identified a novel disease locus for squamous cell carcinoma at 9p21 (CDKN2A/p16(INK4A)/p14(ARF)/CDKN2B/p15(INK4B)/ANRIL; rs1333040, P = 3.0 × 10(-7)) which was replicated in a series of 5415 Han Chinese (P = 0.03; combined analysis, P = 2.3 × 10(-8)). This large analysis provides additional evidence for the role of inherited genetic susceptibility to lung cancer and insight into biological differences in the development of the different histological types of lung cancer.
International Agency for Research on Cancer, Lyon, France.
Maria N
MN
Timofeeva
Rayjean J
RJ
Hung
Thorunn
T
Rafnar
David C
DC
Christiani
John K
JK
Field
Heike
H
Bickeböller
Angela
A
Risch
James D
JD
McKay
Yufei
Y
Wang
Juncheng
J
Dai
Valerie
V
Gaborieau
John
J
McLaughlin
Darren
D
Brenner
Steven A
SA
Narod
Neil E
NE
Caporaso
Demetrius
D
Albanes
Michael
M
Thun
Timothy
T
Eisen
H-Erich
HE
Wichmann
Albert
A
Rosenberger
Younghun
Y
Han
Wei
W
Chen
Dakai
D
Zhu
Margaret
M
Spitz
Xifeng
X
Wu
Mala
M
Pande
Yang
Y
Zhao
David
D
Zaridze
Neonilia
N
Szeszenia-Dabrowska
Jolanta
J
Lissowska
Peter
P
Rudnai
Eleonora
E
Fabianova
Dana
D
Mates
Vladimir
V
Bencko
Lenka
L
Foretova
Vladimir
V
Janout
Hans E
HE
Krokan
Maiken Elvestad
ME
Gabrielsen
Frank
F
Skorpen
Lars
L
Vatten
Inger
I
Njølstad
Chu
C
Chen
Gary
G
Goodman
Mark
M
Lathrop
Simone
S
Benhamou
Tõnu
T
Vooder
Kristjan
K
Välk
Mari
M
Nelis
Andres
A
Metspalu
Olaide
O
Raji
Ying
Y
Chen
John
J
Gosney
Triantafillos
T
Liloglou
Thomas
T
Muley
Hendrik
H
Dienemann
Gudmar
G
Thorleifsson
Hongbing
H
Shen
Kari
K
Stefansson
Paul
P
Brennan
Christopher I
CI
Amos
Richard
R
Houlston
Maria Teresa
MT
Landi
D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People / Q000235:genetics