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Association of the genetic diversity of killer cell immunoglobulin-like receptor genes and HLA-C ligand in Saudi women with breast cancer

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Abstract

Breast cancer (BC) progression and metastases have been linked to antitumor immunity inefficiency and particularly to natural killer (NK) cells. Killer cell immunoglobulin-like receptors (KIRs) are the most polymorphic receptors of NK cells. Through their interactions with human leukocyte antigen (HLA)-C ligands, they modulate NK and T cell actions against target cells. Therefore, we studied the combinatorial effect of KIR genes and their HLA-C ligands on the susceptibility to development of BC in Saudi women. The presence of KIR genes and HLA-C1 and HLA-C2 groups was typed in 50 Saudi patients living in Riyadh and 65 healthy controls using polymerase chain reaction with sequence-specific primers. Our results indicated a protective effect by the KIR2DS2, 2DS3, and 2DL5A genes against BC (OR = 0.25, 0.21, and 0.27, respectively, and p < 0.01). The synergistic action of the three genes was observed when they occurred together, and the absence of the three genes increased BC occurrence by 6.5-fold. Distribution of the HLA-C1/C2 ligand between patients and controls showed an increase in the risk of BC occurrence for the heterozygote C1/C2 (OR = 2.33; 95 % CI = 1.08–5.02; p = 0.037) and a protective effect of the homozygote C2C2 (OR = 0.03; 95 % CI = 0.009–0.098; p < 0.001). Combinatory analyses of KIR genes and their HLA-C ligands showed protective effects of KIR2DL2 and 2DL3 in the absence of their HLA-C1 ligand. These results suggested that KIR-gene content combined with their ligand could influence the risk of BC development in women in Saudi Arabia.

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Acknowledgments

The authors acknowledge the Distinguished Scientist Fellowship Program at King Saud University for financial support for this work.

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Authors and Affiliations

  1. Zoology Department, College of Sciences, King Saud University, Post Office Box 2455, Riyadh, 11451, Saudi Arabia

    Suliman Y. Alomar, Afrah Alkhuriji, Paul Trayhyrn & Lamjed Mansour

  2. Clore Laboratory, Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham, UK

    Paul Trayhyrn

  3. Department of Microbiology/Pathology, King Khalid University Hospital, College of Medicine King Saud University, Riyadh, Saudi Arabia

    Abdulkarim Alhetheel

  4. Immunology and HLA section, Pathology and Clinical Laboratory Medicine, King Fahad Medical City, Riyadh, Saudi Arabia

    Abdullah Al-jurayyan

  5. Faculty of Sciences of Gabès, University of Gabès, Erriadh City, 6072, Zrig Gabès, Tunisia

    Lamjed Mansour

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  1. Suliman Y. Alomar
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  2. Afrah Alkhuriji
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  3. Paul Trayhyrn
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  4. Abdulkarim Alhetheel
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  5. Abdullah Al-jurayyan
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Correspondence to Lamjed Mansour.

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Alomar, S.Y., Alkhuriji, A., Trayhyrn, P. et al. Association of the genetic diversity of killer cell immunoglobulin-like receptor genes and HLA-C ligand in Saudi women with breast cancer. Immunogenetics 69, 69–76 (2017). https://doi.org/10.1007/s00251-016-0950-x

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  • DOI: https://doi.org/10.1007/s00251-016-0950-x

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