Advanced

HLA and KIR Associations of Cervical Neoplasia

Bao, Xiao; Hanson, Aimee L.; Madeleine, Margaret M.; Wang, Sophia S.; Schwartz, Stephen M.; Newell, Felicity; Pettersson-Kymmer, Ulrika; Hemminki, Kari LU ; Tiews, Sven and Steinberg, Winfried, et al. (2018) In The Journal of infectious diseases 218(12). p.2006-2015
Abstract

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 13858 healthy controls of European decent. Results: The following 4 novel HLA alleles were identified in association with... (More)

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 13858 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.

(Less)
Please use this url to cite or link to this publication:
@article{05e4559f-ae73-4504-898d-69a15b8424a4,
  abstract     = {<p>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 13858 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.</p>},
  author       = {Bao, Xiao and Hanson, Aimee L. and Madeleine, Margaret M. and Wang, Sophia S. and Schwartz, Stephen M. and Newell, Felicity and Pettersson-Kymmer, Ulrika and Hemminki, Kari and Tiews, Sven and Steinberg, Winfried and Rader, Janet S. and Castro, Felipe and Safaeian, Mahboobeh and Franco, Eduardo L. and Coutlée, François and Ohlsson, Claes and Cortes, Adrian and Marshall, Mhairi and Mukhopadhyay, Pamela and Cremin, Katie and Johnson, Lisa G. and Garland, Suzanne M. and Tabrizi, Sepehr N. and Wentzensen, Nicolas and Sitas, Freddy and Trimble, Cornelia and Little, Julian and Cruickshank, Maggie and Frazer, Ian H. and Hildesheim, Allan and Brown, Matthew A. and Duncan, Emma L. and Sun, Ying Pu and Leo, Paul J.},
  issn         = {1537-6613},
  language     = {eng},
  month        = {12},
  number       = {12},
  pages        = {2006--2015},
  publisher    = {Oxford University Press},
  series       = {The Journal of infectious diseases},
  title        = {HLA and KIR Associations of Cervical Neoplasia},
  url          = {http://dx.doi.org/10.1093/infdis/jiy483},
  volume       = {218},
  year         = {2018},
}