Immunogenetics

, Volume 62, Issue 11–12, pp 761–765 | Cite as

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

  • Maureen P. Martin
  • Ingrid B. Borecki
  • Zhengyan Zhang
  • Loan Nguyen
  • Duanduan Ma
  • Xiaojiang Gao
  • Ying Qi
  • Mary Carrington
  • Janet S. Rader
Brief Communication

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.

Keywords

Cervical neoplasia HPV HLA KIR 

Notes

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.

Supplementary material

251_2010_477_MOESM1_ESM.docx (20 kb)
Supplementary Table 1 Association of KIR with ICC/CIN3 (DOCX 29 kb)
251_2010_477_MOESM2_ESM.docx (20 kb)
Supplementary Table 2 Association of HLA-Bw with ICC/CIN3 (DOCX 29 kb)
251_2010_477_MOESM3_ESM.docx (24 kb)
Supplementary Table 3 Association of rs9264942 with ICC/CIN3 (DOCX 29 kb)

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Maureen P. Martin
    • 1
  • Ingrid B. Borecki
    • 2
  • Zhengyan Zhang
    • 3
  • Loan Nguyen
    • 3
  • Duanduan Ma
    • 2
  • Xiaojiang Gao
    • 1
  • Ying Qi
    • 1
  • Mary Carrington
    • 1
    • 4
  • Janet S. Rader
    • 2
    • 3
    • 5
  1. 1.Cancer and Inflammation Program, Laboratory of Experimental ImmunologySAIC-Frederick, Inc. NCI-FrederickFrederickUSA
  2. 2.Department of GeneticsWashington University School of MedicineSt. LouisUSA
  3. 3.Department of Obstetrics and GynecologyWashington University School of MedicineSt. LouisUSA
  4. 4.Ragon Institute of Massachusetts General HospitalMassachusetts Institute of Technology and Harvard UniversityBostonUSA
  5. 5.Department of Obstetrics and GynecologyMedical College of WisconsinMilwaukeeUSA

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