A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma.
Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of lung cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types, genotyping 515,922 single-nucleotide polymorphisms (SNPs) in 5739 lung cancer cases and 5848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from ten additional studies, for a total of 13,300 cases and 19,666 controls of European descent. Four studies also provided histology data for replication, resulting in 3333 adenocarcinomas (AD), 2589 squamous cell carcinomas (SQ), and 1418 small cell carcinomas (SC). In analyses by histology, rs2736100 (TERT), on chromosome 5p15.33, was associated with risk of adenocarcinoma (odds ratio [OR]=1.23, 95% confidence interval [CI]=1.13-1.33, p=3.02x10(-7)), but not with other histologic types (OR=1.01, p=0.84 and OR=1.00, p=0.93 for SQ and SC, respectively). This finding was confirmed in each replication study and overall meta-analysis (OR=1.24, 95% CI=1.17-1.31, p=3.74x10(-14) for AD; OR=0.99, p=0.69 and OR=0.97, p=0.48 for SQ and SC, respectively). Other previously reported association signals on 15q25 and 6p21 were also refined, but no additional loci reached genome-wide significance. In conclusion, a lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma.
Landi
Maria Teresa
MT
Division of Cancer Epidemiology, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. landim@mail.nih.gov
Chatterjee
Nilanjan
N
Yu
Kai
K
Goldin
Lynn R
LR
Goldstein
Alisa M
AM
Rotunno
Melissa
M
Mirabello
Lisa
L
Jacobs
Kevin
K
Wheeler
William
W
Yeager
Meredith
M
Bergen
Andrew W
AW
Li
Qizhai
Q
Consonni
Dario
D
Pesatori
Angela C
AC
Wacholder
Sholom
S
Thun
Michael
M
Diver
Ryan
R
Oken
Martin
M
Virtamo
Jarmo
J
Albanes
Demetrius
D
Wang
Zhaoming
Z
Burdette
Laurie
L
Doheny
Kimberly F
KF
Pugh
Elizabeth W
EW
Laurie
Cathy
C
Brennan
Paul
P
Hung
Rayjean
R
Gaborieau
Valerie
V
McKay
James D
JD
Lathrop
Mark
M
McLaughlin
John
J
Wang
Ying
Y
Tsao
Ming-Sound
MS
Spitz
Margaret R
MR
Wang
Yufei
Y
Krokan
Hans
H
Vatten
Lars
L
Skorpen
Frank
F
Arnesen
Egil
E
Benhamou
Simone
S
Bouchard
Christine
C
Metspalu
Andres
A
Metsapalu
Andres
A
Vooder
Tonu
T
Nelis
Mari
M
Välk
Kristian
K
Field
John K
JK
Chen
Chu
C
Goodman
Gary
G
Sulem
Patrick
P
Thorleifsson
Gudmar
G
Rafnar
Thorunn
T
Eisen
Timothy
T
Sauter
Wiebke
W
Rosenberger
Albert
A
Bickeböller
Heike
H
Risch
Angela
A
Chang-Claude
Jenny
J
Wichmann
H Erich
HE
Stefansson
Kari
K
Houlston
Richard
R
Amos
Christopher I
CI
Fraumeni
Joseph F
JF
Savage
Sharon A
SA
Bertazzi
Pier Alberto
PA
Tucker
Margaret A
MA
Chanock
Stephen
S
Caporaso
Neil E
NE
D000230:Adenocarcinoma / Q000235:genetics*; D016022:Case-Control Studies; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000235:genetics*; D015201:Meta-Analysis as Topic; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics