Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population.
To find additional susceptibility loci for lung cancer, we tested promising associations from our previous genome-wide association study (GWAS) of lung cancer in the Chinese population in an extended validation sample size of 7,436 individuals with lung cancer (cases) and 7,483 controls. We found genome-wide significant (P < 5.0 × 10(-8)) evidence for three additional lung cancer susceptibility loci at 10p14 (rs1663689, close to GATA3, P = 2.84 × 10(-10)), 5q32 (rs2895680 in PPP2R2B-STK32A-DPYSL3, P = 6.60 × 10(-9)) and 20q13.2 (rs4809957 in CYP24A1, P = 1.20 × 10(-8)). We also found consistent associations for rs247008 at 5q31.1 (IL3-CSF2-P4HA2, P = 7.68 × 10(-8)) and rs9439519 at 1p36.32 (AJAP1-NPHP4, P = 3.65 × 10(-6)). Four of these loci showed evidence for interactions with smoking dose (P = 1.72 × 10(-10), P = 5.07 × 10(-3), P = 6.77 × 10(-3) and P = 4.49 × 10(-2) for rs2895680, rs4809957, rs247008 and rs9439519, respectively). These results advance our understanding of lung cancer susceptibility and highlight potential pathways that integrate genetic variants and smoking in the development of lung cancer.
Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
Jing
J
Dong
Zhibin
Z
Hu
Chen
C
Wu
Huan
H
Guo
Baosen
B
Zhou
Jiachun
J
Lv
Daru
D
Lu
Kexin
K
Chen
Yongyong
Y
Shi
Minjie
M
Chu
Cheng
C
Wang
Ruyang
R
Zhang
Juncheng
J
Dai
Yue
Y
Jiang
Songyu
S
Cao
Zhenzhen
Z
Qin
Dianke
D
Yu
Hongxia
H
Ma
Guangfu
G
Jin
Jianhang
J
Gong
Chongqi
C
Sun
Xueying
X
Zhao
Zhihua
Z
Yin
Lei
L
Yang
Zhiqiang
Z
Li
Qifei
Q
Deng
Jiucun
J
Wang
Wei
W
Wu
Hong
H
Zheng
Guoquan
G
Zhou
Hongyan
H
Chen
Peng
P
Guan
Zhihang
Z
Peng
Yijiang
Y
Chen
Yongqian
Y
Shu
Lin
L
Xu
Xiangyang
X
Liu
Li
L
Liu
Pin
P
Xu
Baohui
B
Han
Chunxue
C
Bai
Yuxia
Y
Zhao
Haibo
H
Zhang
Ying
Y
Yan
Christopher I
CI
Amos
Feng
F
Chen
Wen
W
Tan
Li
L
Jin
Tangchun
T
Wu
Dongxin
D
Lin
Hongbing
H
Shen
D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D050990:GATA3 Transcription Factor / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D054648:Protein Phosphatase 2 / Q000235:genetics; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase
C102926:DPYSL3 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; C505936:PPP2R2B protein, human; D054648:Protein Phosphatase 2