PMID- 27285765
OWN - NLM
STAT- MEDLINE
DCOM- 20180115
LR  - 20221207
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 27
DP  - 2016 Jul 5
TI  - Pooled analysis of genome-wide association studies of cervical intraepithelial 
      neoplasia 3 (CIN3) identifies a new susceptibility locus.
PG  - 42216-42224
LID - 10.18632/oncotarget.9916 [doi]
AB  - 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-B*07:02, -B*15:01, -DRB1*13:01, -DRB1*15:01, -DQA1*01:03, 
      -DQB1*06:03 and -DQB1*06:02. 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-C*07:02 to be associated with risk of CIN3. The present 
      study provides new insights into pathogenesis of CIN3.
FAU - Chen, Dan
AU  - Chen D
AD  - Ministry of Education and Shanghai Key Laboratory of Children's Environmental 
      Health, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
AD  - Department of Immunology, Genetics and Pathology, Science for Life Laboratory 
      Uppsala, Uppsala University, Uppsala, Sweden.
FAU - Enroth, Stefan
AU  - Enroth S
AD  - Department of Immunology, Genetics and Pathology, Science for Life Laboratory 
      Uppsala, Uppsala University, Uppsala, Sweden.
FAU - Liu, Han
AU  - Liu H
AD  - Ministry of Education and Shanghai Key Laboratory of Children's Environmental 
      Health, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Sun, Yang
AU  - Sun Y
AD  - Laboratory of Biochemistry and Molecular Biology, School of Life Science,Yunnan 
      University, Kunming, China.
FAU - Wang, Huibo
AU  - Wang H
AD  - Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
FAU - Yu, Min
AU  - Yu M
AD  - Laboratory of Biochemistry and Molecular Biology, School of Life Science,Yunnan 
      University, Kunming, China.
FAU - Deng, Lian
AU  - Deng L
AD  - Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max 
      Planck Independent Research Group on Population Genomics, CAS-MPG Partner 
      Institute for Computational Biology (PICB), Shanghai Institutes for Biological 
      Sciences, CAS, Shanghai, China.
AD  - University of Chinese Academy of Sciences, Beijing, China.
FAU - Xu, Shuhua
AU  - Xu S
AD  - Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max 
      Planck Independent Research Group on Population Genomics, CAS-MPG Partner 
      Institute for Computational Biology (PICB), Shanghai Institutes for Biological 
      Sciences, CAS, Shanghai, China.
AD  - University of Chinese Academy of Sciences, Beijing, China.
AD  - School of Life Science and Technology, Shanghai Tech University, Shanghai, China.
AD  - Collaborative Innovation Center of Genetics and Development, Shanghai, China.
FAU - Gyllensten, Ulf
AU  - Gyllensten U
AD  - Department of Immunology, Genetics and Pathology, Science for Life Laboratory 
      Uppsala, Uppsala University, Uppsala, Sweden.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*07 antigen)
RN  - 0 (HLA-B7 Antigen)
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Alleles
MH  - Case-Control Studies
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Genome, Human
MH  - *Genome-Wide Association Study
MH  - Genotype
MH  - HLA-B Antigens/genetics
MH  - HLA-B7 Antigen/genetics
MH  - HLA-DQ alpha-Chains/genetics
MH  - HLA-DQ beta-Chains/genetics
MH  - HLA-DRB1 Chains/genetics
MH  - Humans
MH  - Polymorphism, Single Nucleotide
MH  - Risk
MH  - Uterine Cervical Neoplasms/*genetics
MH  - Uterine Cervical Dysplasia/*genetics
PMC - PMC5173129
OTO - NOTNLM
OT  - cervical intraepithelial neoplasia 3
OT  - expression quantitative trait locus
OT  - genetic variants
OT  - genome-wide association study
OT  - human leukocyte antigen
COIS- Conflicts of Interest: None declared.
EDAT- 2016/06/11 06:00
MHDA- 2018/01/16 06:00
PMCR- 2016/07/05
CRDT- 2016/06/11 06:00
PHST- 2015/12/15 00:00 [received]
PHST- 2016/05/13 00:00 [accepted]
PHST- 2016/06/11 06:00 [pubmed]
PHST- 2018/01/16 06:00 [medline]
PHST- 2016/06/11 06:00 [entrez]
PHST- 2016/07/05 00:00 [pmc-release]
AID - 9916 [pii]
AID - 10.18632/oncotarget.9916 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Jul 5;7(27):42216-42224. doi: 10.18632/oncotarget.9916.