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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
HLA and KIR associations of cervical neoplasia
Journal of Infectious Diseases, Volume 218, No. 12, Year 2018
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Description
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 recognized 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 single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13 858 healthy controls of European decent. Results. The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [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). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .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. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Madeleine, Margaret M.
United States, Seattle
Fred Hutchinson Cancer Center
Wang, Sophia S.
United States, Duarte
City of Hope National Med Center
Schwartz, Stephen Marc
United States, Seattle
Fred Hutchinson Cancer Center
Pettersson-Kymmer, Ulrika
Sweden, Umea
Umeå Universitet
Hemminki, Kari
Sweden, Lund
Lunds Universitet
Rader, Janet S.
United States, Milwaukee
Medical College of Wisconsin
Safaeian, Mahboobeh
United States, Rockville
National Cancer Institute Nci
Franco, Eduardo Luis Fabiano
Canada, Montreal
Université Mcgill
Coutlée, François
Canada, Montreal
Centre Hospitalier de L'universite de Montreal
Ohlsson, Claes
Sweden, Gothenburg
Göteborgs Universitet
Cortés, Adrián
Australia, Brisbane
The University of Queensland
Marshall, Mhairi S.
Australia, Brisbane
Queensland University of Technology
Cremin, Katie
Australia, Brisbane
The University of Queensland
Garland, Suzanne Marie
Australia, Melbourne
University of Melbourne
Australia, Melbourne
Murdoch Children's Research Institute
Tabrizi, Sepehr N.
Australia, Melbourne
University of Melbourne
Australia, Melbourne
Murdoch Children's Research Institute
Wentzensen, Nicolas A.
United States, Rockville
National Cancer Institute Nci
Sitas, F.
Australia, Woolloomooloo
Cancer Council Nsw
Australia, Sydney
The University of Sydney
Australia, Sydney
Unsw Sydney
Trimble, Cornelia Liu
United States, Baltimore
Johns Hopkins University
Little, Julian H.
Canada, Ottawa
University of Ottawa
Hildesheim, Allan
United States, Rockville
National Cancer Institute Nci
Brown, Matthew A.
Australia, Brisbane
Queensland University of Technology
Duncan, Prof Emma L.
Australia, Brisbane
Queensland University of Technology
Leo, Paul J.
Australia, Brisbane
Queensland University of Technology
Statistics
Citations: 18
Authors: 23
Affiliations: 22
Identifiers
Doi:
10.1093/infdis/jiy483
ISSN:
00221899
Research Areas
Cancer
Genetics And Genomics
Study Design
Case-Control Study
Participants Gender
Female