International Lung Cancer Consortium: coordinated association study of 10 potential lung cancer susceptibility variants.
BACKGROUND
Analysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the International Lung Cancer Consortium (ILCCO), we conducted a coordinated genotyping study of 10 common variants selected because of their prior evidence of an association with lung cancer. These variants belonged to candidate genes from different cancer-related pathways including inflammation (IL1B), folate metabolism (MTHFR), regulatory function (AKAP9 and CAMKK1), cell adhesion (SEZL6) and apoptosis (FAS, FASL, TP53, TP53BP1 and BAT3).


METHODS
Genotype data from 15 ILCCO case-control studies were available for a total of 8431 lung cancer cases and 11 072 controls of European descent and Asian ethnic groups. Unconditional logistic regression was used to model the association between each variant and lung cancer risk.


RESULTS
Only the association between a non-synonymous variant of TP53BP1 (rs560191) and lung cancer risk was significant (OR = 0.91, P = 0.002). This association was more striking for squamous cell carcinoma (OR = 0.86, P = 6 x 10(-4)). No heterogeneity by center, ethnicity, smoking status, age group or sex was observed. In order to confirm this association, we included results for this variant from a set of independent studies (9966 cases/11,722 controls) and we reported similar results. When combining all these studies together, we reported an overall OR = 0.93 (0.89-0.97) (P = 0.001). This association was significant only for squamous cell carcinoma [OR = 0.89 (0.85-0.95), P = 1 x 10(-4)].


CONCLUSIONS
This study suggests that rs560191 is associated to lung cancer risk and further highlights the value of consortia in replicating or refuting published genetic associations.
Truong
Therese
T
International Agency for Research on Cancer, Lyon 69008, France.
Sauter
Wiebke
W
McKay
James D
JD
Hosgood
H Dean
HD
Gallagher
Carla
C
Amos
Christopher I
CI
Spitz
Margaret
M
Muscat
Joshua
J
Lazarus
Philip
P
Illig
Thomas
T
Wichmann
H Erich
HE
Bickeböller
Heike
H
Risch
Angela
A
Dienemann
Hendrik
H
Zhang
Zuo-Feng
ZF
Naeim
Behnaz Pezeshki
BP
Yang
Ping
P
Zienolddiny
Shanbeh
S
Haugen
Aage
A
Le Marchand
Loïc
L
Hong
Yun-Chul
YC
Kim
Jin Hee
JH
Duell
Eric J
EJ
Andrew
Angeline S
AS
Kiyohara
Chikako
C
Shen
Hongbing
H
Matsuo
Keitaro
K
Suzuki
Takeshi
T
Seow
Adeline
A
Ng
Daniel P K
DP
Lan
Qing
Q
Zaridze
David
D
Szeszenia-Dabrowska
Neonilia
N
Lissowska
Jolanta
J
Rudnai
Peter
P
Fabianova
Eleonora
E
Constantinescu
Vali
V
Bencko
Vladimir
V
Foretova
Lenka
L
Janout
Vladimir
V
Caporaso
Neil E
NE
Albanes
Demetrius
D
Thun
Michael
M
Landi
Maria Teresa
MT
Trubicka
Joanna
J
Lener
Marcin
M
Lubinski
Jan
J
Wang
Ying
Y
Chabrier
Amélie
A
Boffetta
Paolo
P
Brennan
Paul
P
Hung
Rayjean J
RJ
D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics; D016017:Odds Ratio; D000071857:Tumor Suppressor p53-Binding Protein 1
C092009:BAG6 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D042965:Methylenetetrahydrofolate Reductase (NADPH2)