The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia.
Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10(-7) or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30 x 10(-11)). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38 x 10(-11)). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60 x 10(-20), allelic risk = 1.54, 95% Confidence Interval (CI) 1.41-1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40-1.87), and 2.35 (95% CI: 1.95-2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.
Hsiung
Chao Agnes
CA
Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan. hsiung@nhri.org.tw
Lan
Qing
Q
Hong
Yun-Chul
YC
Chen
Chien-Jen
CJ
Hosgood
H Dean
HD
Chang
I-Shou
IS
Chatterjee
Nilanjan
N
Brennan
Paul
P
Wu
Chen
C
Zheng
Wei
W
Chang
Gee-Chen
GC
Wu
Tangchun
T
Park
Jae Yong
JY
Hsiao
Chin-Fu
CF
Kim
Yeul Hong
YH
Shen
Hongbing
H
Seow
Adeline
A
Yeager
Meredith
M
Tsai
Ying-Huang
YH
Kim
Young Tae
YT
Chow
Wong-Ho
WH
Guo
Huan
H
Wang
Wen-Chang
WC
Sung
Sook Whan
SW
Hu
Zhibin
Z
Chen
Kuan-Yu
KY
Kim
Joo Hyun
JH
Chen
Ying
Y
Huang
Liming
L
Lee
Kyoung-Mu
KM
Lo
Yen-Li
YL
Gao
Yu-Tang
YT
Kim
Jin Hee
JH
Liu
Li
L
Huang
Ming-Shyan
MS
Jung
Tae Hoon
TH
Jin
Guangfu
G
Caporaso
Neil
N
Yu
Dianke
D
Kim
Chang Ho
CH
Su
Wu-Chou
WC
Shu
Xiao-Ou
XO
Xu
Ping
P
Kim
In-San
IS
Chen
Yuh-Min
YM
Ma
Hongxia
H
Shen
Min
M
Cha
Sung Ick
SI
Tan
Wen
W
Chang
Chin-Hao
CH
Sung
Jae Sook
JS
Zhang
Mingfeng
M
Yang
Tsung-Ying
TY
Park
Kyong Hwa
KH
Yuenger
Jeff
J
Wang
Chih-Liang
CL
Ryu
Jeong-Seon
JS
Xiang
Yongbing
Y
Deng
Qifei
Q
Hutchinson
Amy
A
Kim
Jun Suk
JS
Cai
Qiuyin
Q
Landi
Maria Teresa
MT
Yu
Chong-Jen
CJ
Park
Ju-Yeon
JY
Tucker
Margaret
M
Hung
Jen-Yu
JY
Lin
Chien-Chung
CC
Perng
Reury-Perng
RP
Boffetta
Paolo
P
Chen
Chih-Yi
CY
Chen
Kun-Chieh
KC
Yang
Shi-Yi
SY
Hu
Chi-Yuan
CY
Chang
Chung-Kai
CK
Fraumeni
Joseph F
JF
Chanock
Stephen
S
Yang
Pan-Chyr
PC
Rothman
Nathaniel
N
Lin
Dongxin
D
D000230:Adenocarcinoma / Q000208:ethnology / Q000235:genetics*; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors