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. 2019 Mar 28;11(4):438.
doi: 10.3390/cancers11040438.

NKG2D Polymorphism in Melanoma Patients from Southeastern Spain

Lourdes Gimeno  1 , Helios Martínez-Banaclocha  2 , M Victoria Bernardo  3 , José Miguel Bolarin  4 , Luis Marín  5 , Ruth López-Hernández  6 , M Rocío López-Alvarez  7 , M Rosa Moya-Quiles  8 , Manuel Muro  9 , José Francisco Frias-Iniesta  10 , Jorge Martínez-Escribano  11 , M Rocío Alvarez-López  12 , Alfredo Minguela  13 , José Antonio Campillo  14
Affiliations

NKG2D Polymorphism in Melanoma Patients from Southeastern Spain

Lourdes Gimeno et al. Cancers (Basel). .

Abstract

Background: Natural killer (NK) and CD8+ T cells are involved in the immune response against melanoma. C-Type lectin-like NK cell receptors are located in the Natural Killer Complex (NKC) region 12p13.2-p12.3 and play a critical role in regulating the activity of NK and CD8+ T cells. An association between polymorphisms in the NKC region, including the NKG2D gene and NKG2A promoter, and the risk of cancer has been previously described. The aim of this study was to analyze the association of polymorphisms in the NKC region with cutaneous melanoma in patients from southeastern Spain.

Methods: Seven single-nucleotide polymorphisms (SNPs) in the NKG2D gene (NKC3,4,7,9,10,11,12), and one SNP in the NKG2A promoter (NKC17) were genotyped by a TaqMan 5' Nuclease Assay in 233 melanoma patients and 200 matched healthy controls.

Results: A linkage disequilibrium analysis of the SNPs performed in the NKC region revealed two blocks of haplotypes (Hb-1 and Hb-2) with 14 and seven different haplotype subtypes, respectively. The third most frequent haplotype from the block Hb-2-NK3 (CAT haplotype)-was significantly more frequent on melanoma patients than on healthy controls (p = 0.00009, Pc = 0.0006). No further associations were found when NKC SNPs were considered independently.

Conclusions: Our results suggest an association between NKG2D polymorphisms and the risk of cutaneous malignant melanoma.

Keywords: Melanoma; NK cell; NKG2A; NKG2D; gene polymorphism.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Linkage disequilibrium analysis between the eight NKC SNPs analyzed in melanoma patients in the Haploview software. (A) The r2 values of the association with each SNP are represented: r2 values > 0.7 (high grade of linkage disequilibrium) in red; r2 values between 0.5 and 0.7 in yellow; and r2 values < 0.5 in blue. (B) The two blocks of SNPs in close linkage are also represented; block Hb-1 including SNPs NKC3, NKC7, NKC11, and NKC12, and block Hb-2 including SNPs NKC4, NKC9, and NKC10.
See this image and copyright information in PMC

References

    1. Rastrelli M., Tropea S., Rossi C.R., Alaibac M. Melanoma: Epidemiology, Risk Factors, Pathogenesis, Diagnosis and Classification. In Vivo. 2014;28:1005–1012. - PubMed
    1. Rigel D.S. Epidemiology of melanoma. Semin. Cutan. Med. Surg. 2010;29:204–209. doi: 10.1016/j.sder.2010.10.005. - DOI - PubMed
    1. Mohammadpour A., Derakhshan M., Darabi H., Hedayat P., Momeni M. Melanoma: Where we are and where we go. J. Cell. Physiol. 2018;234:3307–3320. doi: 10.1002/jcp.27286. - DOI - PubMed
    1. Anichini A., Vegetti C., Mortarini R. The paradox of T cell-mediated antitumor immunity in spite of poor clinical outcome in human melanoma. Cancer Immunol. Immunother. 2004;53:855–864. doi: 10.1007/s00262-004-0526-8. - DOI - PMC - PubMed
    1. Lee P.P., Yee C., Savage P.A., Fong L., Brockstedt D., Weber J.S., Johnson D., Swetter S., Thompson J., Greenberg P.D., et al. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat. Med. 1999;5:677–685. doi: 10.1038/9525. - DOI - PubMed