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  • Pettersson-Kymmer, UlrikaUmeå University,Umeå universitet,Farmakologi,Näringsforskning (author)

HLA and KIR Associations of Cervical Neoplasia

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-08-07
  • Oxford University Press,2018
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-151134
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-151134URI
  • https://doi.org/10.1093/infdis/jiy483DOI
  • https://lup.lub.lu.se/record/05e4559f-ae73-4504-898d-69a15b8424a4URI
  • https://gup.ub.gu.se/publication/273945URI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Background: Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognised by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk.Methods: Here, we used HLA and KIR dosages imputed from SNP genotype data from 2,143 cervical neoplasia cases and 13,858 healthy controls of European decent.Results: Four novel HLA alleles were identified in association with cervical neoplasia: HLA-DRB3*9901 (OR=1.24, P=2.49×10-9), HLA-DRB5*0101 (OR=1.29, P=2.26×10-8), HLA-DRB5*9901 (OR=0.77, P=1.90×10-9) and HLA-DRB3*0301 (OR=0.63, P=4.06×10-5), due to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles. We also found homozygosity of HLA-C1 group alleles is a protective factor for HPV16-related cervical neoplasia (C1/C1, OR=0.79, P=0.005). This protective association was restricted to carriers of either KIR2DL2 (OR=0.67, P=0.00045) or KIR2DS2 (OR=0.69, P=0.0006).Conclusions: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.

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  • Hanson, Aimee LPrincess Alexandra Hospital,University of Queensland (author)
  • Madeleine, Margaret MFred Hutchinson Cancer Research Center,Queensland University of Technology,University of Melbourne,Murdoch Children's Research Institute (author)
  • Wang, Sophia SCity of Hope National Medical Center (author)
  • Schwartz, Stephen M (author)
  • Newell, FelicityQueensland University of Technology (author)
  • Pettersson-Kymmer, Ulrika (author)
  • Hemminki, KariLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,German Cancer Research Centre(Swepub:lu)med-khk (author)
  • Tiews, SvenMVZ Labor für Cytopathologie Dr. Steinberg GmbH (author)
  • Steinberg, WinfriedMVZ Labor für Cytopathologie Dr. Steinberg GmbH (author)
  • Rader, Janet SMedical College of Wisconsin (author)
  • Castro, FelipeGerman Cancer Research Centre (author)
  • Safaeian, MahboobehNational Cancer Institute, NCI (author)
  • Franco, Eduardo LMcGill University (author)
  • Coutlée, FrançoisUniversity Of Montreal Health Center (CRCHUM) (author)
  • Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,University of Gothenburg,Centre for Bone and Arthritis Research,Institutionen för medicin,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xohlcl (author)
  • Cortes, AdrianUniversity of Queensland (author)
  • Marshall, Mhairi (author)
  • Mukhopadhyay, PamelaUniversity of Queensland (author)
  • Cremin, KatieUniversity of Queensland (author)
  • Johnson, Lisa GFred Hutchinson Cancer Research Center (author)
  • Garland, Suzanne M (author)
  • Tabrizi, Sepehr NMurdoch Children's Research Institute,University of Melbourne (author)
  • Wentzensen, NicolasNational Cancer Institute, NCI (author)
  • Sitas, FreddyCancer Council New South Wales,University of New South Wales,University of Sydney (author)
  • Trimble, CorneliaJohns Hopkins University (author)
  • Little, JulianUniversity of Ottawa (author)
  • Cruickshank, MaggieUniversity of Aberdeen (author)
  • Frazer, Ian HUniversity of Queensland,Princess Alexandra Hospital (author)
  • Hildesheim, AllanNational Cancer Institute, NCI (author)
  • Brown, Matthew AQueensland University of Technology (author)
  • Duncan, Emma LQueensland University of Technology (author)
  • Sun, YingPu (author)
  • Leo, Paul JQueensland University of Technology (author)
  • Bao, XiaoFirst Affiliated Hospital of Zhengzhou University,Queensland University of Technology (author)
  • Sun, Ying PuFirst Affiliated Hospital of Zhengzhou University (author)
  • Umeå universitetFarmakologi (creator_code:org_t)

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