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Published in: Medical Oncology 2/2012

01-06-2012 | Original Paper

Killer cell immunoglobulin-like receptor genes in patients with breast cancer

Authors: Ozlem Goruroglu Ozturk, Faik Deniz Gun, Gurbuz Polat

Published in: Medical Oncology | Issue 2/2012

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Abstract

Killer cell immunoglobulin-like receptors (KIRs) contribute to the pathogenesis of diverse kind of diseases. Previous studies have shown associations between KIR genes, their ligands and either protection or susceptibility to leukemias or virally associated solid tumors. However, the possible roles of KIR gene polymorphisms in the development of breast cancer remain largely unknown. To investigate the association of KIR gene polymorphisms with breast cancer, we carried out the present study on 33 breast cancer patients and 77 healthy controls by means of sequence-specific oligonucleotide probes analysis, and then all data were statistically analyzed by Fisher exact test. Our results showed that the frame genes KIR2DL4, 3DL2, 3DL3, and 3DP1 were found in all patients and all controls. The rate of activating KIR2DS1 was much higher in patients with breast cancer than that in healthy controls (P = 0.032) while the allelic types of activating 2DS4 (2DS4*003/4/6/7) were lower in patients with breast cancer compared with healthy controls (P = 0.028). Additionally, there was a statistically significant negative correlation between 2DL1 genes and breast cancer development (P = 0.025). In conclusion, this study suggests that the activating KIR2DS1 may trigger breast cancer development, while 2DL1 gene and 2DS4*003/4/6/7 alleles are possibly protectors for breast cancer.
Literature
1.
go back to reference Khong HT, Restifo NP. Natural selection of tumor variants in the generation of “tumor escape” phenotypes. Nat Immunol. 2002;3:999–1005.PubMedCrossRef Khong HT, Restifo NP. Natural selection of tumor variants in the generation of “tumor escape” phenotypes. Nat Immunol. 2002;3:999–1005.PubMedCrossRef
3.
go back to reference Ljunggren HG, Karre K. In search of the ‘missing self’. MHC molecules and NK cell recognition. Immunol Today. 1990;11:237–44.PubMedCrossRef Ljunggren HG, Karre K. In search of the ‘missing self’. MHC molecules and NK cell recognition. Immunol Today. 1990;11:237–44.PubMedCrossRef
4.
go back to reference Vilches C, Parham P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol. 2002;20:217–51.PubMedCrossRef Vilches C, Parham P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol. 2002;20:217–51.PubMedCrossRef
6.
go back to reference Bao X, et al. An allelic typing method for 2DS4 variant used in study of haplotypes of killer cell immunoglobulin-like receptor gene. Int J Lab Hematol. 2010;32:625–32.PubMedCrossRef Bao X, et al. An allelic typing method for 2DS4 variant used in study of haplotypes of killer cell immunoglobulin-like receptor gene. Int J Lab Hematol. 2010;32:625–32.PubMedCrossRef
7.
go back to reference Early Breast Cancer Trialists’ Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15 year survival: an overview of the randomised trials. Lancet 2005;365:1687–1717. Early Breast Cancer Trialists’ Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15 year survival: an overview of the randomised trials. Lancet 2005;365:1687–1717.
8.
go back to reference Madigan MP, Ziegler RG, Benichou J, Byrne C, Hoover RN. Proportion of breast cancer cases in the United States explained by well-established risk factors. J Natl Cancer Inst. 1995;87:1681–5.PubMedCrossRef Madigan MP, Ziegler RG, Benichou J, Byrne C, Hoover RN. Proportion of breast cancer cases in the United States explained by well-established risk factors. J Natl Cancer Inst. 1995;87:1681–5.PubMedCrossRef
9.
10.
go back to reference Turnbull C, Hodgson S. Genetic predisposition to cancer. Clin Med. 2005;5:491–8.PubMed Turnbull C, Hodgson S. Genetic predisposition to cancer. Clin Med. 2005;5:491–8.PubMed
11.
go back to reference Algarra I, Garcia-Lora A, Cabrera T, Ruiz-Cabello F, Garrido F. The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape. Cancer Immunol Immunother. 2004;53:904–10.PubMedCrossRef Algarra I, Garcia-Lora A, Cabrera T, Ruiz-Cabello F, Garrido F. The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape. Cancer Immunol Immunother. 2004;53:904–10.PubMedCrossRef
12.
go back to reference Cabrera T, et al. High frequency of altered HLA class I phenotypes in invasive breast carcinomas. Hum Immunol. 1996;50:127–34.PubMedCrossRef Cabrera T, et al. High frequency of altered HLA class I phenotypes in invasive breast carcinomas. Hum Immunol. 1996;50:127–34.PubMedCrossRef
13.
go back to reference Khakoo SI, Carrington M. KIR and disease: a model system or system of models? Immunol Rev. 2006;214:186–201.PubMedCrossRef Khakoo SI, Carrington M. KIR and disease: a model system or system of models? Immunol Rev. 2006;214:186–201.PubMedCrossRef
14.
go back to reference Carlsten M, Malmberg KJ, Ljunggren HG. Natural killer cell-mediated lysis of freshly isolated human tumor cells. Int J Cancer. 2009;124:757–62.PubMedCrossRef Carlsten M, Malmberg KJ, Ljunggren HG. Natural killer cell-mediated lysis of freshly isolated human tumor cells. Int J Cancer. 2009;124:757–62.PubMedCrossRef
15.
go back to reference Boyton RJ, Altmann DM. Natural killer cells, killer immunoglobulin-like receptors and human leucocyte antigen class I in disease. Clin Exp Immunol. 2007;149:1–8.PubMedCrossRef Boyton RJ, Altmann DM. Natural killer cells, killer immunoglobulin-like receptors and human leucocyte antigen class I in disease. Clin Exp Immunol. 2007;149:1–8.PubMedCrossRef
16.
go back to reference Möller P, Hammerling GJ. The role of surface HLA-A, B, C molecules in tumour immunity. Cancer Surv. 1992;13:101–27.PubMed Möller P, Hammerling GJ. The role of surface HLA-A, B, C molecules in tumour immunity. Cancer Surv. 1992;13:101–27.PubMed
17.
go back to reference Yawata M, et al. MHC class I-specific inhibitory receptors and their ligands structure diverse human NK cell repertoires toward a balance of missing self-response. Blood. 2008;112:2369–80.PubMedCrossRef Yawata M, et al. MHC class I-specific inhibitory receptors and their ligands structure diverse human NK cell repertoires toward a balance of missing self-response. Blood. 2008;112:2369–80.PubMedCrossRef
18.
go back to reference Jonsson AH, Yokoyama WM. Natural killer cell tolerance licensing and other mechanisms. Adv Immunol. 2009;101:27–79.PubMedCrossRef Jonsson AH, Yokoyama WM. Natural killer cell tolerance licensing and other mechanisms. Adv Immunol. 2009;101:27–79.PubMedCrossRef
19.
go back to reference Kulkarni S, Martin MP, Carrington M. The yin and yang of HLA and KIR in human disease. Semin Immunol. 2008;20:343–52.PubMedCrossRef Kulkarni S, Martin MP, Carrington M. The yin and yang of HLA and KIR in human disease. Semin Immunol. 2008;20:343–52.PubMedCrossRef
20.
go back to reference Carrington M, et al. Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci. J Exp Med. 2005;201:1069–75.PubMedCrossRef Carrington M, et al. Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci. J Exp Med. 2005;201:1069–75.PubMedCrossRef
21.
go back to reference Naumova E, et al. Genetic polymorphism of NK receptors and their ligands in melanoma patients: prevalence of inhibitory over activating signals. Cancer Immunol Immunother. 2005;54:172–8.PubMedCrossRef Naumova E, et al. Genetic polymorphism of NK receptors and their ligands in melanoma patients: prevalence of inhibitory over activating signals. Cancer Immunol Immunother. 2005;54:172–8.PubMedCrossRef
22.
go back to reference Zhang Y. Killer cell immunoglobulin-like receptor gene polymorphisms in patients with leukemia: Possible association with susceptibility to the disease. Leukemia res. 2010;34:55–8.CrossRef Zhang Y. Killer cell immunoglobulin-like receptor gene polymorphisms in patients with leukemia: Possible association with susceptibility to the disease. Leukemia res. 2010;34:55–8.CrossRef
23.
go back to reference Besson C, et al. Association of killer cell immunoglobulin-like receptor genes with Hodgkin’s lymphoma in a familial study. PLoS One. 2007;2:e406.PubMedCrossRef Besson C, et al. Association of killer cell immunoglobulin-like receptor genes with Hodgkin’s lymphoma in a familial study. PLoS One. 2007;2:e406.PubMedCrossRef
24.
go back to reference Butsch Kovacic M, et al. Variation of the killer cell immunoglobulin-like receptors and HLA-C genes in nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2005;14:2673–7.PubMedCrossRef Butsch Kovacic M, et al. Variation of the killer cell immunoglobulin-like receptors and HLA-C genes in nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2005;14:2673–7.PubMedCrossRef
25.
go back to reference Bahler DW, Hartung L, Hill S, Bowen GM, Vonderheid EC. CD158 k/KIR3DL2 is a useful marker for identifying neoplastic T-cells in Sezary syndrome by flow cytometry. Cytometry B Clin Cytom. 2008;74:156–62.PubMed Bahler DW, Hartung L, Hill S, Bowen GM, Vonderheid EC. CD158 k/KIR3DL2 is a useful marker for identifying neoplastic T-cells in Sezary syndrome by flow cytometry. Cytometry B Clin Cytom. 2008;74:156–62.PubMed
26.
go back to reference Morice WG, Kurtin PJ, Leibson PJ, Tefferi A, Hanson CA. Demonstration of aberrant T-cell and natural killer-cell antigen expression in all cases of granular lymphocytic leukaemia. Br J Haematol. 2003;120:1026–36.PubMedCrossRef Morice WG, Kurtin PJ, Leibson PJ, Tefferi A, Hanson CA. Demonstration of aberrant T-cell and natural killer-cell antigen expression in all cases of granular lymphocytic leukaemia. Br J Haematol. 2003;120:1026–36.PubMedCrossRef
27.
go back to reference Nowakowski GS, Morice WG, Phyliky RL, Li CY, Tefferi A. Human leucocyte antigen class I and killer immunoglobulin-like receptor expression patterns in T-cell large granular lymphocyte leukaemia. Br J Haematol. 2005;128:490–2.PubMedCrossRef Nowakowski GS, Morice WG, Phyliky RL, Li CY, Tefferi A. Human leucocyte antigen class I and killer immunoglobulin-like receptor expression patterns in T-cell large granular lymphocyte leukaemia. Br J Haematol. 2005;128:490–2.PubMedCrossRef
28.
go back to reference Lopez-Vazquez A, et al. Protective effect of the HLA-Bw4I80 epitope and the Killer Cell Immunoglobulin-Like Receptor 3DS1 gene against the development of hepatocellular carcinoma in patients with hepatitis C virus infection. J Infect Dis. 2005;192:162–5.PubMedCrossRef Lopez-Vazquez A, et al. Protective effect of the HLA-Bw4I80 epitope and the Killer Cell Immunoglobulin-Like Receptor 3DS1 gene against the development of hepatocellular carcinoma in patients with hepatitis C virus infection. J Infect Dis. 2005;192:162–5.PubMedCrossRef
29.
go back to reference Al Omar S. Associations between genes for killer immunoglobulin-like receptors and their ligands in patients with solid tumors. Hum Immunol. 2010;71:976–81.PubMedCrossRef Al Omar S. Associations between genes for killer immunoglobulin-like receptors and their ligands in patients with solid tumors. Hum Immunol. 2010;71:976–81.PubMedCrossRef
Metadata
Title
Killer cell immunoglobulin-like receptor genes in patients with breast cancer
Authors
Ozlem Goruroglu Ozturk
Faik Deniz Gun
Gurbuz Polat
Publication date
01-06-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-9932-x

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