International Lung Cancer Consortium: pooled analysis of sequence variants in DNA repair and cell cycle pathways.
BACKGROUND
The International Lung Cancer Consortium was established in 2004. To clarify the role of DNA repair genes in lung cancer susceptibility, we conducted a pooled analysis of genetic variants in DNA repair pathways, whose associations have been investigated by at least 3 individual studies.


METHODS
Data from 14 studies were pooled for 18 sequence variants in 12 DNA repair genes, including APEX1, OGG1, XRCC1, XRCC2, XRCC3, ERCC1, XPD, XPF, XPG, XPA, MGMT, and TP53. The total number of subjects included in the analysis for each variant ranged from 2,073 to 13,955 subjects.


RESULTS
Four of the variants were found to be weakly associated with lung cancer risk with borderline significance: these were XRCC3 T241M [heterozygote odds ratio (OR), 0.89; 95% confidence interval (95% CI), 0.79-0.99 and homozygote OR, 0.84; 95% CI, 0.71-1.00] based on 3,467 cases and 5,021 controls from 8 studies, XPD K751Q (heterozygote OR, 0.99; 95% CI, 0.89-1.10 and homozygote OR, 1.19; 95% CI, 1.02-1.39) based on 6,463 cases and 6,603 controls from 9 studies, and TP53 R72P (heterozygote OR, 1.14; 95% CI, 1.00-1.29 and homozygote OR, 1.20; 95% CI, 1.02-1.42) based on 3,610 cases and 5,293 controls from 6 studies. OGG1 S326C homozygote was suggested to be associated with lung cancer risk in Caucasians (homozygote OR, 1.34; 95% CI, 1.01-1.79) based on 2,569 cases and 4,178 controls from 4 studies but not in Asians. The other 14 variants did not exhibit main effects on lung cancer risk.


CONCLUSIONS
In addition to data pooling, future priorities of International Lung Cancer Consortium include coordinated genotyping and multistage validation for ongoing genome-wide association studies.
Hung
Rayjean J
RJ
IARC, 150 cours Albert Thomas, 69008 Lyon, France.
Christiani
David C
DC
Risch
Angela
A
Popanda
Odilia
O
Haugen
Aage
A
Zienolddiny
Shan
S
Benhamou
Simone
S
Bouchardy
Christine
C
Lan
Qing
Q
Spitz
Margaret R
MR
Wichmann
H-Erich
HE
LeMarchand
Loic
L
Vineis
Paolo
P
Matullo
Giuseppe
G
Kiyohara
Chikako
C
Zhang
Zuo-Feng
ZF
Pezeshki
Benhnaz
B
Harris
Curtis
C
Mechanic
Leah
L
Seow
Adeline
A
Ng
Daniel P K
DP
Szeszenia-Dabrowska
Neonila
N
Zaridze
David
D
Lissowska
Jolanta
J
Rudnai
Peter
P
Fabianova
Eleonora
E
Mates
Dana
D
Foretova
Lenka
L
Janout
Vladimir
V
Bencko
Vladimir
V
Caporaso
Neil
N
Chen
Chu
C
Duell
Eric J
EJ
Goodman
Gary
G
Field
John K
JK
Houlston
Richard S
RS
Hong
Yun-Chul
YC
Landi
Maria Teresa
MT
Lazarus
Philip
P
Muscat
Joshua
J
McLaughlin
John
J
Schwartz
Ann G
AG
Shen
Hongbing
H
Stucker
Isabelle
I
Tajima
Kazuo
K
Matsuo
Keitaro
K
Thun
Michael
M
Yang
Ping
P
Wiencke
John
J
Andrew
Angeline S
AS
Monnier
Stephanie
S
Boffetta
Paolo
P
Brennan
Paul
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins