A Novel Genetic Variant in Long Non-coding RNA Gene NEXN-AS1 is Associated with Risk of Lung Cancer

被引：33

作者：

Yuan, Hua ^{[1
,2
,3
,4
]}

Liu, Hongliang ^{[3
,4
]}

Liu, Zhensheng ^{[3
,4
]}

Owzar, Kouros ^{[4
,5
]}

Han, Younghun ^{[6
]}

Su, Li ^{[7
,8
]}

Wei, Yongyue ^{[7
,8
]}

Hung, Rayjean J. ^{[9
]}

McLaughlin, John ^{[10
]}

Brhane, Yonathan ^{[9
]}

Brennan, Paul ^{[11
]}

Bickeboeller, Heike ^{[12
]}

Rosenberger, Albert ^{[12
]}

Houlston, Richard S. ^{[13
]}

Caporaso, Neil ^{[14
]}

Landi, Maria Teresa ^{[14
]}

Heinrich, Joachim ^{[15
,16
]}

Risch, Angela ^{[17
,18
,19
]}

Christiani, David C. ^{[7
,8
]}

Gumus, Zeynep H. ^{[20
]}

Klein, Robert J. ^{[20
]}

Amos, Christopher I. ^{[6
]}

Wei, Qingyi ^{[3
,4
]}

机构：

[1] Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Nanjing, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Affiliated Hosp Stomatol, Dept Oral & Maxillofacial Surg, Nanjing, Jiangsu, Peoples R China

[3] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA

[4] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA

[5] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA

[6] Dartmouth Coll, Geisel Sch Med, Community & Family Med, Hanover, NC USA

[7] Massachusetts Gen Hosp, Boston, MA 02114 USA

[8] Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA

[9] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada

[10] Publ Hlth Ontario, Toronto, ON, Canada

[11] Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France

[12] Univ Gottingen, Univ Med Ctr, Dept Genet Epidemiol, Gottingen, Germany

[13] Inst Canc Res, Div Genet & Epidemiol, London, England

[14] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[15] Inst Epidemiol 1, German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Neuherberg, Germany

[16] Univ Munich, Univ Hosp Munich, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany

[17] Salzburg Univ, Dept Mol Biol, Salzburg, Austria

[18] DKFZ German Canc Res Ctr, Dept Epigenom & Canc Risk Factors, Heidelberg, Germany

[19] German Ctr Lung Res DZL, TLRC H, Heidelberg, Germany

[20] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; SUSCEPTIBILITY LOCUS; POOLED ANALYSIS; METAANALYSIS; REPLICATION; SURVIVAL; CATALOG; DISEASE; 5P15.33;

D O I：

10.1038/srep34234

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Lung cancer etiology is multifactorial, and growing evidence has indicated that long non-coding RNAs (lncRNAs) are important players in lung carcinogenesis. We performed a large-scale meta-analysis of 690,564 SNPs in 15,531 autosomal lncRNAs by using datasets from six previously published genome-wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium in populations of European ancestry. Previously unreported significant SNPs (P value < 1 x 10(-7)) were further validated in two additional independent lung cancer GWAS datasets from Harvard University and deCODE. In the final meta-analysis of all eight GWAS datasets with 17,153 cases and 239,337 controls, a novel risk SNP rs114020893 in the lncRNA NEXN-AS1 region at 1p31.1 remained statistically significant (odds ratio = 1.17; 95% confidence interval = 1.11-1.24; P = 8.31 x 10(-9)). In further in silico analysis, rs114020893 was predicted to change the secondary structure of the lncRNA. Our finding indicates that SNP rs114020893 of NEXN-AS1 at 1p31.1 may contribute to lung cancer susceptibility.

引用

页数：8

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