Genome-Wide Association Study Identifies a Novel Susceptibility Locus at 12q23.1 for Lung Squamous Cell Carcinoma in Han Chinese

被引：24

作者：

Dong, Jing ^{[1
,2
,3
,4
]}

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

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

Guo, Huan ^{[8
,9
]}

Zhou, Baosen ^{[10
]}

Lv, Jiachun ^{[11
]}

Lu, Daru ^{[12
,13
]}

Shi, Yongyong ^{[14
,15
]}

Shu, Yongqian ^{[16
]}

Xu, Lin ^{[17
]}

Chu, Minjie ^{[1
,2
]}

Wang, Cheng ^{[1
,2
]}

Zhang, Ruyang ^{[1
,2
]}

Dai, Juncheng ^{[1
,2
]}

Jiang, Yue ^{[1
,2
]}

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

Ma, Hongxia ^{[1
,2
]}

Zhao, Xueying ^{[12
,13
]}

Yin, Zhihua ^{[10
]}

Yang, Lei ^{[11
]}

Li, Zhiqiang ^{[14
,15
]}

Deng, Qifei ^{[8
,9
]}

Cao, Songyu ^{[1
,2
]}

Qin, Zhenzhen ^{[1
,2
]}

Gong, Jianhang ^{[1
,2
]}

Sun, Chongqi ^{[1
,2
]}

Wang, Jiucun ^{[12
,13
]}

Wu, Wei ^{[10
]}

Zhou, Guoquan ^{[14
,15
]}

Chen, Hongyan ^{[12
,13
]}

Guan, Peng ^{[10
]}

Chen, Yijiang ^{[16
]}

Liu, Xiangyang ^{[7
,18
]}

Liu, Li ^{[19
]}

Xu, Pin ^{[20
]}

Han, Baohui ^{[21
]}

Bai, Chunxue ^{[22
]}

Zhao, Yuxia ^{[23
]}

Zhang, Haibo ^{[24
]}

Yan, Ying ^{[24
]}

Liu, Jibin ^{[25
]}

Amos, Christopher I. ^{[26
]}

Chen, Feng ^{[1
,2
]}

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

Jin, Li ^{[12
,13
]}

Wu, Tangchun ^{[8
,9
]}

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

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

Shen, Hongbing ^{[1
,2
,3
,4
]}

机构：

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

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

[3] Nanjing Med Univ, Clin Epidemiol Sect, 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, 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, Wuhan 430074, Peoples R China

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

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

[11] Guangzhou Med Univ, State Key Lab Resp Dis, Inst Chem Carcinogenesis, 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, Sch Life Sci, MOE Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China

[14] Shanghai Jiao Tong Univ, Biox Ctr, Shanghai 200030, Peoples R China

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

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

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

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

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

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

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

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

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

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

[25] Nantong Canc Hosp, Dept Surg, Nantong, Peoples R China

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

来源：

PLOS GENETICS | 2013年 / 9卷 / 01期

基金：

中国国家自然科学基金;

关键词：

GENETIC-VARIANTS; CANCER; ADENOCARCINOMA; RISK; EXPRESSION; SMOKING; PROGRESSION; MECHANISMS; JAPANESE; 5P15.33;

D O I：

10.1371/journal.pgen.1003190

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Adenocarcinoma (AC) and squamous cell carcinoma (SqCC) are two major histological subtypes of lung cancer. Genome-wide association studies (GWAS) have made considerable advances in the understanding of lung cancer susceptibility. Obvious heterogeneity has been observed between different histological subtypes of lung cancer, but genetic determinants in specific to lung SqCC have not been systematically investigated. Here, we performed the GWAS analysis specifically for lung SqCC in 833 SqCC cases and 3,094 controls followed by a two-stage replication in additional 2,223 lung SqCC cases and 6,409 controls from Chinese populations. We found that rs12296850 in SLC17A8-NR1H4 gene region at12q23.1 was significantly associated with risk of lung SqCC at genome-wide significance level [additive model: odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.72-0.84, P = 1.19610(-10)]. Subjects carrying AG or GG genotype had a 26% (OR = 0.74, 95% CI = 0.67-0.81) or 32% (OR = 0.68, 95% CI = 0.56-0.83) decreased risk of lung SqCC, respectively, as compared with AA genotype. However, we did not observe significant association between rs12296850 and risk of lung AC in a total of 4,368 cases with lung AC and 9,486 controls (OR = 0.96, 95% CI = 0.90-1.02, P = 0.173). These results indicate that genetic variations on chromosome 12q23.1 may specifically contribute to lung SqCC susceptibility in Chinese population.

引用

页数：7

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