uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Pooled analysis of genome-wide association studies of cervical intraepithelial neoplasia 3 (CIN3) identifies a new susceptibility locus
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab. Shanghai Jiao Tong Univ, Sch Med, Xin Hua Hosp, Minist Educ, Shanghai, Peoples R China.;Shanghai Jiao Tong Univ, Sch Med, Xin Hua Hosp, Shanghai Key Lab Childrens Environm Hlth, Shanghai, Peoples R China..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-5056-9137
Shanghai Jiao Tong Univ, Sch Med, Xin Hua Hosp, Minist Educ, Shanghai, Peoples R China.;Shanghai Jiao Tong Univ, Sch Med, Xin Hua Hosp, Shanghai Key Lab Childrens Environm Hlth, Shanghai, Peoples R China..
Yunnan Univ, Sch Life Sci, Lab Biochem & Mol Biol, Kunming, Peoples R China..
Show others and affiliations
2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 27, 42216-42224 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 7, no 27, 42216-42224 p.
Keyword [en]
cervical intraepithelial neoplasia 3, genome-wide association study, genetic variants, expression quantitative trait locus, human leukocyte antigen
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-308265DOI: 10.18632/oncotarget.9916ISI: 000380942600099PubMedID: 27285765OAI: oai:DiVA.org:uu-308265DiVA: diva2:1049311
Available from: 2016-11-24 Created: 2016-11-24 Last updated: 2016-11-24Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Enroth, StefanGyllensten, Ulf
By organisation
Medicinsk genetik och genomikScience for Life Laboratory, SciLifeLab
In the same journal
OncoTarget
Cancer and OncologyCell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 66 hits
ReferencesLink to record
Permanent link

Direct link