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HLA-Cw group 1 ligands for KIR increase susceptibility to invasive cervical cancer

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Abstract

Inherited genetic polymorphisms within immune response genes have been shown to associate with risk of invasive cervical cancer (ICC) and its immediate precursor, cervical intraepithelial neoplasia grade 3. Here, we used the transmission/disequilibrium test to detect disease-liability alleles and investigate haplotype transmission of KIR and HLA class I polymorphisms in a large family-based population of women with cervical cancer and their biological parents (359 trios). The effect of distinct human papillomavirus types was also explored. HLA-Cw group 1 (HLA-Cw alleles with asparagine at position 80), which serves as ligand for certain killer immunoglobulin-like receptors (KIR), was significantly overtransmitted in women with ICC (P = 0.04), and particularly in the subgroup of women infected with high risk HPV16 or 18 subtypes (P = 0.008). These data support the involvement of the HLA-C locus in modulating the risk of cervical neoplasia perhaps through its function as ligands for KIR, but functional studies are essential to confirm this hypothesis.

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References

  • Arnheim L, Dillner J, Sanjeevi CB (2005) A population-based cohort study of KIR genes and genotypes in relation to cervical intraepithelial neoplasia. Tissue Antigens 65:252–259

    Article  CAS  PubMed  Google Scholar 

  • Balkwill F, Charles KA, Mantovani A (2005) Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7:211–217

    Article  CAS  PubMed  Google Scholar 

  • Belinson S, Smith JS, Myers E, Olshan A, Belinson J, Pretorius R, Qiao YL, Hartmann K (2008) Descriptive evidence that risk profiles for cervical intraepithelial neoplasia 1, 2, and 3 are unique. Cancer Epidemiol Biomarkers Prev 17:2350–2355

    Article  PubMed  Google Scholar 

  • Bosch FX, de Sanjose S (2007) The epidemiology of human papillomavirus infection and cervical cancer. Dis Markers 23:213–227

    PubMed  Google Scholar 

  • Cardon LR, Palmer LJ (2003) Population stratification and spurious allelic association. Lancet 361:598–604

    Article  PubMed  Google Scholar 

  • Carrington M, Martin MP, van Bergen J (2008) KIR-HLA intercourse in HIV disease. Trends Microbiol 16:620–627

    Article  CAS  PubMed  Google Scholar 

  • Carrington M, Wang S, Martin MP, Gao X, Schiffman M, Cheng J, Herrero R, Rodriguez AC, Kurman R, Mortel R, Schwartz P, Glass A, Hildesheim A (2005) Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci. J Exp Med 201:1069–1075

    Article  CAS  PubMed  Google Scholar 

  • Chaturvedi AK, Madeleine MM, Biggar RJ, Engels EA (2009) Risk of human papillomavirus-associated cancers among persons with AIDS. J Natl Cancer Inst 101:1120–1130

    Article  PubMed  Google Scholar 

  • Clayton D (1999) A generalization of the transmission/disequilibrium test for uncertain-haplotype transmission. Am J Hum Genet 65:1170–1177

    Article  CAS  PubMed  Google Scholar 

  • Clayton D, Jones H (1999) Transmission/disequilibrium tests for extended marker haplotypes. Am J Hum Genet 65:1161–1169

    Article  CAS  PubMed  Google Scholar 

  • Clayton J, Lonjou C (1997) Allele and haplotype frequencies for HLA loci in various ethnic groups. In: Charron D (ed) Genetic Diversity of HLA. Functional and Medical Implication, pp. 668-820. Medical and Scientific International, Paris

    Google Scholar 

  • Coleman N, Birley HD, Renton AM, Hanna NF, Ryait BK, Byrne M, Taylor-Robinson D, Stanley MA (1994) Immunological events in regressing genital warts. Am J Clin Pathol 102:768–774

    CAS  PubMed  Google Scholar 

  • de Visser KE, Eichten A, Coussens LM (2006) Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 6:24–37

    Article  PubMed  Google Scholar 

  • De Vuyst H, Lillo F, Broutet N, Smith JS (2008) HIV, human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy. Eur J Cancer Prev 17:545–554

    Article  PubMed  Google Scholar 

  • Doorbar J (2006) Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci (Lond) 110:525–541

    Article  CAS  Google Scholar 

  • Fellay J, Shianna KV, Ge D, Colombo S, Ledergerber B, Weale M, Zhang K, Gumbs C, Castagna A, Cossarizza A, Cozzi-Lepri A, De Luca A, Easterbrook P, Francioli P, Mallal S, Martinez-Picado J, Miro JM, Obel N, Smith JP, Wyniger J, Descombes P, Antonarakis SE, Letvin NL, McMichael AJ, Haynes BF, Telenti A, Goldstein DB (2007) A whole-genome association study of major determinants for host control of HIV-1. Science 317:944–947

    Article  CAS  PubMed  Google Scholar 

  • Freedman ML, Reich D, Penney KL, McDonald GJ, Mignault AA, Patterson N, Gabriel SB, Topol EJ, Smoller JW, Pato CN, Pato MT, Petryshen TL, Kolonel LN, Lander ES, Sklar P, Henderson B, Hirschhorn JN, Altshuler D (2004) Assessing the impact of population stratification on genetic association studies. Nat Genet 36:388–393

    Article  CAS  PubMed  Google Scholar 

  • IARC Working Group (1995) Human papillomaviruses. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans 64:1–378

  • Koopman LA, Corver WE, van der Slik AR, Giphart MJ, Fleuren GJ (2000) Multiple genetic alterations cause frequent and heterogeneous human histocompatibility leukocyte antigen class I loss in cervical cancer. J Exp Med 191:961–976

    Article  CAS  PubMed  Google Scholar 

  • Koshiol J, Lindsay L, Pimenta JM, Poole C, Jenkins D, Smith JS (2008) Persistent human papillomavirus infection and cervical neoplasia: a systematic review and meta-analysis. Am J Epidemiol 168:123–137

    Article  PubMed  Google Scholar 

  • Kulkarni S, Martin MP, Carrington M (2008) The Yin and Yang of HLA and KIR in human disease. Semin Immunol 20:343–352

    Article  CAS  PubMed  Google Scholar 

  • Li J, Gerhard DS, Zhang Z, Huettner PC, Wright J, Nguyen L, Lu D, Rader JS (2003) Denaturing high-performance liquid chromatography for detecting and typing genital human papillomavirus. J Clin Microbiol 41:5563–5571

    Article  CAS  PubMed  Google Scholar 

  • Long EO, Rajagopalan S (2000) HLA class I recognition by killer cell Ig-like receptors. Semin Immunol 12:101–108

    Article  CAS  PubMed  Google Scholar 

  • Martin MP, Carrington M (2008) KIR locus polymorphisms: genotyping and disease association analysis. Methods Mol Biol 415:49–64

    Article  CAS  PubMed  Google Scholar 

  • Neuman RJ, Huettner PC, Li L, Mardis ER, Duffy BF, Wilson RK, Rader JS (2000) Association between DQB1 and cervical cancer in patients with human papillomavirus and family controls. Obstet Gynecol 95:134–140

    Article  CAS  PubMed  Google Scholar 

  • Reyburn H, Mandelboim O, Vales-Gomez M, Sheu EG, Pazmany L, Davis DM, Strominger JL (1997) Human NK cells: their ligands, receptors and functions. Immunol Rev 155:119–125

    Article  CAS  PubMed  Google Scholar 

  • Stranger BE, Forrest MS, Clark AG, Minichiello MJ, Deutsch S, Lyle R, Hunt S, Kahl B, Antonarakis SE, Tavare S, Deloukas P, Dermitzakis ET (2005) Genome-wide associations of gene expression variation in humans. PLoS Genet 1:e78

    Article  PubMed  Google Scholar 

  • Stranger BE, Nica AC, Forrest MS, Dimas A, Bird CP, Beazley C, Ingle CE, Dunning M, Flicek P, Koller D, Montgomery S, Tavare S, Deloukas P, Dermitzakis ET (2007) Population genomics of human gene expression. Nat Genet 39:1217–1224

    Article  CAS  PubMed  Google Scholar 

  • Thomas R, Apps R, Qi Y, Gao X, Male V, O'HUigin C, O'Connor G, Ge D, Fellay J, Martin JN, Margolick J, Goedert JJ, Buchbinder S, Kirk GD, Martin MP, Telenti A, Deeks SG, Walker BD, Goldstein D, McVicar DW, Moffett A, Carrington M (2009) HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C. Nat Genet 41:1290–1294

    Article  CAS  PubMed  Google Scholar 

  • Wang SS, Hildesheim A, Gao X, Schiffman M, Herrero R, Bratti MC, Sherman ME, Barnes WA, Greenberg MD, McGowan L, Mortel R, Schwartz PE, Zaino RJ, Glass AG, Burk RD, Karacki P, Carrington M (2002a) Comprehensive analysis of human leukocyte antigen class I alleles and cervical neoplasia in 3 epidemiologic studies. J Infect Dis 186:598–605

    Article  CAS  PubMed  Google Scholar 

  • Wang SS, Hildesheim A, Gao X, Schiffman M, Herrero R, Bratti MC, Sherman ME, Barnes WA, Greenberg MD, McGowan L, Mortel R, Schwartz PE, Zaino RJ, Glass AG, Burk RD, Karacki P, Carrington M (2002b) Human leukocyte antigen class I alleles and cervical neoplasia: no heterozygote advantage. Cancer Epidemiol Biomarkers Prev 11:419–420

    PubMed  Google Scholar 

  • Wang SS, Wheeler CM, Hildesheim A, Schiffman M, Herrero R, Bratti MC, Sherman ME, Alfaro M, Hutchinson ML, Morales J, Lorincz A, Burk RD, Carrington M, Erlich HA, Apple RJ (2001) Human leukocyte antigen class I and II alleles and risk of cervical neoplasia: results from a population-based study in Costa Rica. J Infect Dis 184:1310–1314

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Borecki I, Nguyen L, Ma D, Smith K, Huettner PC, Mutch DG, Herzog TJ, Gibb RK, Powell MA, Grigsby PW, Massad LS, Hernandez E, Judson PL, Swisher EM, Crowder S, Li J, Gerhard DS, Rader JS (2007) CD83 gene polymorphisms increase susceptibility to human invasive cervical cancer. Cancer Res 67:11202–11208

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by National Cancer Institute grants 5R01CA094141 and 5R01CA095713. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

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Author notes

  1. Janet S. Rader

    Present address: Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA

Authors and Affiliations

  1. Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc. NCI-Frederick, Frederick, MD, 21702, USA

    Maureen P. Martin, Xiaojiang Gao, Ying Qi & Mary Carrington

  2. Department of Genetics, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Ingrid B. Borecki, Duanduan Ma & Janet S. Rader

  3. Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Zhengyan Zhang, Loan Nguyen & Janet S. Rader

  4. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA, 02114, USA

    Mary Carrington

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  1. Maureen P. Martin
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  9. Janet S. Rader
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Corresponding author

Correspondence to Janet S. Rader.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary Table 1

Association of KIR with ICC/CIN3 (DOCX 29 kb)

Supplementary Table 2

Association of HLA-Bw with ICC/CIN3 (DOCX 29 kb)

Supplementary Table 3

Association of rs9264942 with ICC/CIN3 (DOCX 29 kb)

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Martin, M.P., Borecki, I.B., Zhang, Z. et al. HLA-Cw group 1 ligands for KIR increase susceptibility to invasive cervical cancer. Immunogenetics 62, 761–765 (2010). https://doi.org/10.1007/s00251-010-0477-5

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  • DOI: https://doi.org/10.1007/s00251-010-0477-5

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