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HLA and KIR Associations of Cervical Neoplasia
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.ORCID iD: 0000-0002-0557-9803
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2018 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 218, no 12, p. 2006-2015Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Oxford University Press, 2018. Vol. 218, no 12, p. 2006-2015
Keywords [en]
Cervical neoplasia; human leukocyte antigens (HLA), killer immunoglobulin-like receptors (KIRs), HPV16-related cervical neoplasia
National Category
Medical and Health Sciences Medical Genetics
Identifiers
URN: urn:nbn:se:umu:diva-151134DOI: 10.1093/infdis/jiy483ISI: 000453672600018PubMedID: 30099516OAI: oai:DiVA.org:umu-151134DiVA, id: diva2:1242412
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Ragnar Söderbergs stiftelseTorsten Söderbergs stiftelseThe Kempe Foundations, JCK-1021Västerbotten County CouncilAvailable from: 2018-08-28 Created: 2018-08-28 Last updated: 2019-05-21Bibliographically approved

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Pettersson-Kymmer, Ulrika

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