PMID- 32580243
OWN - NLM
STAT- MEDLINE
DCOM- 20210419
LR  - 20210419
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 147
IP  - 9
DP  - 2020 Nov 1
TI  - Association of genomic variants at the human leukocyte antigen locus with 
      cervical cancer risk, HPV status and gene expression levels.
PG  - 2458-2468
LID - 10.1002/ijc.33171 [doi]
AB  - The human leukocyte antigen (HLA) locus on chromosome 6 has been reported to be 
      associated with cervical cancer. We investigated two independent 
      single-nucleotide polymorphisms in a large case-control series of cervical 
      dysplasia and carcinoma that has been newly established by the German Cervigen 
      Consortium, comprising a total of 2481 cases and 1556 healthy females. We find 
      significant associations for both variants, rs9272117 at HLA-DQA1 and rs2844511 
      at MICA and HCP5, with cervical disease. Both variants showed evidence of 
      association with invasive cervical cancer (rs9272117: OR 0.89, 95% CI 0.79-0.99, 
      P = .036; rs2844511: OR 1.17, 95% CI 1.04-1.31, P = .008) and with high-grade 
      dysplasia (rs9272117: OR 0.78, 95% CI 0.70-0.87, P = 7.1 x 10(-6) ; rs2844511: OR 
      1.13, 95% CI 1.01-1.26, P = .035), as well as in a combined analysis of both 
      groups (rs9272117: OR 0.83, 95% CI 0.75-0.91, P = 6.9 x 10(-5) ; rs2844511: OR 
      1.14, 95% CI 1.04-1.26, P = .005). Variant rs2844511, but not rs9272117, also 
      showed modest evidence of association with low-grade dysplasia (OR 1.26, 95% CI 
      1.04-1.54, P = .019). In case-only analyses, rs2844511 tended to predict HPV 
      status (P = .044) and rs9272117 tended to associate with HPV16 (P = .022). RNA 
      studies in cervical samples showed a significant correlation in the transcript 
      levels of MICA, HCP5 and HLA-DQA1, suggesting extensive co-regulation. All three 
      genes were upregulated in HPV16-positive samples. In stratified analyses, 
      rs9272117 was associated with HLA-DQA1 levels, specifically in HPV-positive 
      samples, while rs2844511 was associated with MICA and HCP5 levels. The risk 
      allele of rs2844511 was required for correlations between MICA or HCP5 with 
      HLA-DQA1. Altogether, our results support 6p21.32-33 as the first consistent 
      cervical cancer susceptibility locus and provide evidence for a link between 
      genetic risk variants, HPV16 status and transcript levels of HLA-DQA1, HCP5 and 
      MICA, which may contribute to tumor immune evasion.
CI  - (c) 2020 The Authors. International Journal of Cancer published by John Wiley & 
      Sons Ltd on behalf of UICC.
FAU - Ramachandran, Dhanya
AU  - Ramachandran D
AD  - Department of Gynaecology, Comprehensive Cancer Center, Hannover Medical School, 
      Hannover, Germany.
FAU - Schurmann, Peter
AU  - Schurmann P
AD  - Department of Gynaecology, Comprehensive Cancer Center, Hannover Medical School, 
      Hannover, Germany.
FAU - Mao, Qianqian
AU  - Mao Q
AD  - Department of Gynaecology, Comprehensive Cancer Center, Hannover Medical School, 
      Hannover, Germany.
FAU - Wang, Yingying
AU  - Wang Y
AD  - Department of Gynaecology, Comprehensive Cancer Center, Hannover Medical School, 
      Hannover, Germany.
FAU - Bretschneider, Lisa-Marie
AU  - Bretschneider LM
AD  - Department of Gynaecology, Comprehensive Cancer Center, Hannover Medical School, 
      Hannover, Germany.
FAU - Speith, Lisa-Marie
AU  - Speith LM
AD  - Department of Gynaecology, Comprehensive Cancer Center, Hannover Medical School, 
      Hannover, Germany.
FAU - Hulse, Fabienne
AU  - Hulse F
AD  - Department of Gynaecology, Comprehensive Cancer Center, Hannover Medical School, 
      Hannover, Germany.
FAU - Enssen, Julia
AU  - Enssen J
AD  - Department of Gynaecology, Comprehensive Cancer Center, Hannover Medical School, 
      Hannover, Germany.
FAU - Bousset, Kristine
AU  - Bousset K
AD  - Department of Gynaecology, Comprehensive Cancer Center, Hannover Medical School, 
      Hannover, Germany.
FAU - Jentschke, Matthias
AU  - Jentschke M
AD  - Department of Gynaecology, Comprehensive Cancer Center, Hannover Medical School, 
      Hannover, Germany.
FAU - Bohmer, Gerd
AU  - Bohmer G
AD  - IZD Hannover, Hannover, Germany.
FAU - Strauss, Hans-Georg
AU  - Strauss HG
AD  - Department of Gynaecology, University Clinics, Martin-Luther University, 
      Halle-Wittenberg, Germany.
FAU - Hirchenhain, Christine
AU  - Hirchenhain C
AD  - Department of Gynaecology, Clinics Carl Gustav Carus, University of Dresden, 
      Dresden, Germany.
FAU - Schmidmayr, Monika
AU  - Schmidmayr M
AD  - Department of Gynaecology, Technische Universitat Munchen, Munich, Germany.
FAU - Tarbiat, Johanna
AU  - Tarbiat J
AD  - Martin-Luther Hospital, Charite University, Berlin, Germany.
FAU - Runnebaum, Ingo
AU  - Runnebaum I
AD  - Department of Gynecology, Jena University Hospital, Friedrich-Schiller-University 
      Jena, Jena, Germany.
FAU - Durst, Matthias
AU  - Durst M
AD  - Department of Gynecology, Jena University Hospital, Friedrich-Schiller-University 
      Jena, Jena, Germany.
FAU - Hein, Alexander
AU  - Hein A
AD  - Department of Gynecology and Obstetrics, Erlangen University Hospital, 
      Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of 
      Erlangen-Nuremberg (FAU), Erlangen, Germany.
FAU - Koch, Martin
AU  - Koch M
AD  - Department of Gynecology and Obstetrics, Erlangen University Hospital, 
      Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of 
      Erlangen-Nuremberg (FAU), Erlangen, Germany.
FAU - Ruebner, Matthias
AU  - Ruebner M
AD  - Department of Gynecology and Obstetrics, Erlangen University Hospital, 
      Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of 
      Erlangen-Nuremberg (FAU), Erlangen, Germany.
FAU - Ekici, Arif
AU  - Ekici A
AD  - Institute of Human Genetics, Friedrich-Alexander University of Erlangen-Nurnberg, 
      Erlangen, Germany.
FAU - Beckmann, Matthias W
AU  - Beckmann MW
AD  - Department of Gynecology and Obstetrics, Erlangen University Hospital, 
      Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of 
      Erlangen-Nuremberg (FAU), Erlangen, Germany.
FAU - Fasching, Peter A
AU  - Fasching PA
AUID- ORCID: 0000-0003-4885-8471
AD  - Department of Gynecology and Obstetrics, Erlangen University Hospital, 
      Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of 
      Erlangen-Nuremberg (FAU), Erlangen, Germany.
FAU - Luyten, Alexander
AU  - Luyten A
AD  - Dysplasia Unit, Department of Gynecology and Obstetrics, Mare Klinikum, 
      Kronshagen, Germany.
AD  - Department of Gynecology, Wolfsburg Hospital, Wolfsburg, Germany.
FAU - Petry, Karl-Ulrich
AU  - Petry KU
AUID- ORCID: 0000-0002-5875-9840
AD  - Department of Gynecology, Wolfsburg Hospital, Wolfsburg, Germany.
FAU - Hillemanns, Peter
AU  - Hillemanns P
AD  - Department of Gynaecology, Comprehensive Cancer Center, Hannover Medical School, 
      Hannover, Germany.
FAU - Dork, Thilo
AU  - Dork T
AUID- ORCID: 0000-0002-9458-0282
AD  - Department of Gynaecology, Comprehensive Cancer Center, Hannover Medical School, 
      Hannover, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200710
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alleles
MH  - Case-Control Studies
MH  - Cervix Uteri/immunology/*pathology/virology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/immunology
MH  - Genetic Loci
MH  - Genetic Predisposition to Disease
MH  - Germany/epidemiology
MH  - HLA Antigens/*genetics/immunology
MH  - Human papillomavirus 16/immunology/isolation & purification
MH  - Humans
MH  - Middle Aged
MH  - Papillomavirus Infections/*epidemiology/genetics/immunology/virology
MH  - Polymorphism, Single Nucleotide
MH  - Tumor Escape/genetics
MH  - Up-Regulation/immunology
MH  - Uterine Cervical Dysplasia/*epidemiology/genetics/immunology/virology
MH  - Uterine Cervical Neoplasms/*epidemiology/genetics/immunology/virology
MH  - Young Adult
OTO - NOTNLM
OT  - HPV infection
OT  - association study
OT  - cervical malignancy
OT  - eQTL
OT  - single nucleotide polymorphism
EDAT- 2020/06/25 06:00
MHDA- 2021/04/20 06:00
CRDT- 2020/06/25 06:00
PHST- 2020/02/19 00:00 [received]
PHST- 2020/05/15 00:00 [revised]
PHST- 2020/05/25 00:00 [accepted]
PHST- 2020/06/25 06:00 [pubmed]
PHST- 2021/04/20 06:00 [medline]
PHST- 2020/06/25 06:00 [entrez]
AID - 10.1002/ijc.33171 [doi]
PST - ppublish
SO  - Int J Cancer. 2020 Nov 1;147(9):2458-2468. doi: 10.1002/ijc.33171. Epub 2020 Jul 
      10.