Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population

被引：123

作者：

Dong, Jing ^{[1
,2
]}

Hu, Zhibin ^{[1
,2
,3
,4
]}

Wu, Chen ^{[5
,6
,7
]}

Guo, Huan ^{[8
,9
]}

Zhou, Baosen ^{[10
]}

Lv, Jiachun ^{[11
]}

Lu, Daru ^{[12
,13
]}

Chen, Kexin ^{[14
]}

Shi, Yongyong

Chu, Minjie ^{[1
,2
]}

Wang, Cheng ^{[1
,2
]}

Zhang, Ruyang ^{[1
,2
]}

Dai, Juncheng ^{[1
,2
]}

Jiang, Yue ^{[1
,2
]}

Cao, Songyu ^{[1
,2
]}

Qin, Zhenzhen ^{[1
,2
]}

Yu, Dianke ^{[5
,6
,7
]}

Ma, Hongxia ^{[1
,2
]}

Jin, Guangfu ^{[1
,2
,3
]}

Gong, Jianhang ^{[1
,2
]}

Sun, Chongqi ^{[1
,2
]}

Zhao, Xueying ^{[12
,13
]}

Yin, Zhihua ^{[10
]}

Yang, Lei ^{[11
]}

Li, Zhiqiang ^{[15
,19
]}

Deng, Qifei ^{[8
,9
]}

Wang, Jiucun ^{[12
,13
]}

Wu, Wei ^{[10
]}

Zheng, Hong ^{[14
]}

Zhou, Guoquan ^{[15
,19
]}

Chen, Hongyan ^{[12
,13
]}

Guan, Peng ^{[10
]}

Peng, Zhihang ^{[1
,2
]}

Chen, Yijiang ^{[16
]}

Shu, Yongqian ^{[16
]}

Xu, Lin ^{[17
]}

Liu, Xiangyang ^{[7
,18
]}

Liu, Li ^{[20
]}

Xu, Pin ^{[21
]}

Han, Baohui ^{[22
]}

Bai, Chunxue ^{[23
]}

Zhao, Yuxia ^{[24
]}

Zhang, Haibo ^{[25
]}

Yan, Ying ^{[25
]}

Amos, Christopher I. ^{[26
]}

Chen, Feng ^{[1
,2
]}

Tan, Wen ^{[5
,6
,7
]}

Jin, Li ^{[12
,13
]}

Wu, Tangchun ^{[8
,9
]}

Lin, Dongxin ^{[5
,6
,7
]}

机构：

[1] Nanjing Med Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Sch Publ Hlth, MOE, Key Lab Modern Toxicol, Nanjing, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Sect Clin Epidemiol, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Ctr Canc, Nanjing, Jiangsu, Peoples R China

[4] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing, Jiangsu, Peoples R China

[5] Chinese Acad Med Sci, State Key Lab Mol Oncol, Canc Inst & Hosp, Beijing 100730, Peoples R China

[6] Chinese Acad Med Sci, Dept Etiol & Carcinogenesis, Canc Inst & Hosp, Beijing 100730, Peoples R China

[7] Peking Union Med Coll, Beijing 100021, Peoples R China

[8] Huazhong Univ Sci & Technol, Inst Occupat Med, Sch Publ Hlth, Tongji Med Coll, Wuhan 430074, Peoples R China

[9] Huazhong Univ Sci & Technol, Minist Educ, Key Lab Environm & Hlth, Sch Publ Hlth,Tongji Med Coll, Wuhan 430074, Peoples R China

[10] China Med Univ, Sch Publ Hlth, Dept Epidemiol, Shenyang, Peoples R China

[11] Guangzhou Med Coll, Inst Chem Carcinogenesis, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China

[12] Fudan Univ, State Key Lab Genet Engn, Ctr Fudan VARI Genet Epidemiol, Shanghai 200433, Peoples R China

[13] Fudan Univ, MOE Key Lab Contemporary Anthropol, Sch Life Sci, Shanghai 200433, Peoples R China

[14] Tianjin Med Univ, Dept Epidemiol & Biostat, Canc Hosp & Inst, Tianjin, Peoples R China

[15] Shanghai Jiao Tong Univ, Bio X Ctr, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Shanghai 200030, Peoples R China

[16] Nanjing Med Univ, Dept Thorac Surg & Oncol, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China

[17] Nanjing Med Univ, Dept Thorac Surg, Affiliated Canc Hosp, Jiangsu Canc Hosp, Nanjing, Jiangsu, Peoples R China

[18] Chinese Acad Med Sci, Dept Thorac Surg, Canc Hosp, Beijing 100730, Peoples R China

[19] Shanghai Jiao Tong Univ, Affiliated Changning Mental Hlth Ctr, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Shanghai 200030, Peoples R China

[20] Huazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Tongji Med Coll, Wuhan 430074, Peoples R China

[21] Corp Staff Worker Hosp, Dept Oncol, Wuhan Iron & Steel Grp, Wuhan, Peoples R China

[22] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Resp Dis, Shanghai 200030, Peoples R China

[23] Fudan Univ, Zhongshan Hosp, Dept Resp Dis, Shanghai 200433, Peoples R China

[24] China Med Univ, Dept Radiat Oncol, Affiliated Hosp 1, Shenyang, Peoples R China

[25] Shenyang No Hosp, Dept Radiotherapy, Shenyang, Peoples R China

[26] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA

来源：

NATURE GENETICS | 2012年 / 44卷 / 08期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; HUMAN GENE-EXPRESSION; CIGARETTE-SMOKE; CELLS; VARIANTS; PROTEIN; 5P15.33; ALPHA; GATA3; GAMMA;

D O I：

10.1038/ng.2351

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To find additional susceptibility loci for lung cancer, we tested promising associations from our previous genome-wide association study (GWAS)(1) 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 x 10(-8)) evidence for three additional lung cancer susceptibility loci at 10p14 (rs1663689, close to GATA3, P = 2.84 x 10(-10)), 5q32 (rs2895680 in PPP2R2B-STK32A-DPYSL3, P = 6.60 x 10(-9)) and 20q13.2 (rs4809957 in CYP24A1, P = 1.20 x 10(-8)). We also found consistent associations for rs247008 at 5q31.1 (IL3-CSF2-P4HA2, P = 7.68 x 10(-8)) and rs9439519 at 1p36.32 (AJAP1-NPHP4, P = 3.65 x 10(-6)). Four of these loci showed evidence for interactions with smoking dose (P = 1.72 x 10(-10), P = 5.07 x 10(-3), P = 6.77 x 10(-3) and P = 4.49 x 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.

引用

页码：895 / +

页数：6

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