Pooled analysis of genome-wide association studies of cervical intraepithelial neoplasia 3 (CIN3) identifies a new susceptibility locus

doi:10.18632/oncotarget.9916

	Pooled analysis of genome-wide association studies of cervical intraepithelial neoplasia 3 (CIN3) identifies a new susceptibility locus
	Chen, Dan 1,2,3; Enroth, Stefan 3; Liu, Han 1,2; Sun, Yang 4; Wang, Huibo 5; Yu, Min 4; Deng, Lian 6; Xu, Shuhua6,7,8,9 ; Gyllensten, Ulf 3
	2016-07-05
发表期刊	ONCOTARGET
ISSN	1949-2553
卷号	7 期号:27 页码:42216-42224
发表状态	已发表
DOI	10.18632/oncotarget.9916
摘要	Recent genome-wide association studies (GWASs) in subjects of European descent have identified associations between cervical cancer risk and three independent loci as well as multiple classical human leukocyte antigen (HLA) alleles at 6p21.3. To search for novel loci associated with development of cervical cancer, we performed a pooled analysis of data from two GWASs by imputing over 10 million genetic variants and 424 classical HLA alleles, for 1,553 intraepithelial neoplasia 3 (CIN3), 81 cervical cancer and 4,442 controls from the Swedish population. Notable findings were validated in an independent study of 961 patients (827 with CIN3 and 123 with cervical cancer) and 1,725 controls. Our data provided increased support for previously identified loci at 6p21.3 (rs9271898, P = 1.2 x 10(-24); rs2516448, 1.1 x 10(-15); and rs3130196, 2.3 x 10(-9), respectively) and also confirmed associations with reported classical HLA alleles including HLA-B07:02, -B15:01, -DRB113:01, -DRB115:01, -DQA101:03, -DQB106:03 and -DQB106:02. In addition, we identified and subsequently replicated an independent signal at rs73730372 at 6p21.3 (odds ratio = 0.60, 95% confidence interval = 0.54-0.67, P = 3.0 x 10(-19)), which was found to be an expression quantitative trait locus (eQTL) of both HLA-DQA1 and HLA-DQB1. This is one of the strongest common genetic protective variants identified so far for CIN3. We also found HLA-C07:02 to be associated with risk of CIN3. The present study provides new insights into pathogenesis of CIN3.
关键词	cervical intraepithelial neoplasia 3 genome-wide association study genetic variants expression quantitative trait locus human leukocyte antigen
收录类别	SCI
语种	英语
资助项目	[QD 2015006]
WOS研究方向	Oncology ; Cell Biology
WOS类目	Oncology ; Cell Biology
WOS记录号	WOS:000380942600099
出版者	IMPACT JOURNALS LLC
WOS关键词	HUMAN-PAPILLOMAVIRUS ; IMMUNE-RESPONSES ; CANCER ; POPULATION ; HLA ; CARCINOGENESIS ; INFECTION ; DISEASE ; GENE
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1781
专题	生命科学与技术学院_特聘教授组_徐书华组
通讯作者	Chen, Dan
作者单位	1.Shanghai Jiao Tong Univ, Sch Med, Xin Hua Hosp, Minist Educ, Shanghai, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Xin Hua Hosp, Shanghai Key Lab Childrens Environm Hlth, Shanghai, Peoples R China 3.Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab Uppsala, Uppsala, Sweden 4.Yunnan Univ, Sch Life Sci, Lab Biochem & Mol Biol, Kunming, Peoples R China 5.Nanjing Med Univ, Dept Neurosurg, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China 6.Chinese Acad Sci, Key Lab Computat Biol, Max Planck Independent Res Grp Populat Genom, CAS MPG Partner Inst Computat Biol PICB,Shanghai, Shanghai, Peoples R China 7.Univ Chinese Acad Sci, Beijing, Peoples R China 8.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 9.Collaborat Innovat Ctr Genet & Dev, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Chen, Dan,Enroth, Stefan,Liu, Han,et al. Pooled analysis of genome-wide association studies of cervical intraepithelial neoplasia 3 (CIN3) identifies a new susceptibility locus[J]. ONCOTARGET,2016,7(27):42216-42224.
APA	Chen, Dan.,Enroth, Stefan.,Liu, Han.,Sun, Yang.,Wang, Huibo.,...&Gyllensten, Ulf.(2016).Pooled analysis of genome-wide association studies of cervical intraepithelial neoplasia 3 (CIN3) identifies a new susceptibility locus.ONCOTARGET,7(27),42216-42224.
MLA	Chen, Dan,et al."Pooled analysis of genome-wide association studies of cervical intraepithelial neoplasia 3 (CIN3) identifies a new susceptibility locus".ONCOTARGET 7.27(2016):42216-42224.