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.
Highlights
The incidence of cutaneous malignant melanoma is increasing worldwide and, it only accounts for 5% of cutaneous malignancies, this tumor is responsible for approximately 75% of all Cancers 2019, 11, 438; doi:10.3390/cancers11040438 www.mdpi.com/journal/cancersCancers 2019, 11, 438 deaths caused by skin cancer [1,2,3]
haplotype block 1 (Hb-1) and haplotype block 2 (Hb-2)
Our results show no association between the risk of developing cutaneous melanoma and the Natural Killer Complex (NKC) single-nucleotide polymorphisms (SNPs) when considered individually
Summary
The incidence of cutaneous malignant melanoma is increasing worldwide and, it only accounts for 5% of cutaneous malignancies, this tumor is responsible for approximately 75% of all Cancers 2019, 11, 438; doi:10.3390/cancers11040438 www.mdpi.com/journal/cancersCancers 2019, 11, 438 deaths caused by skin cancer [1,2,3]. The effector functions of NK and CD8+ T cells are regulated by a balance of signals delivered by activating and inhibitory receptors that interact with their cognate ligands expressed on infected or transformed cells [12,13,14], including malignant melanocytes [9,15]. In this context, it should be noted that the NK cell-mediated killing of melanoma cells is controlled by multiple activating receptors/ligands [10,16,17,18], among which the NKG2D receptor/NKG2D ligand interaction plays an important role and induces one of the most important signals leading to the lysis of melanoma tumor cells [9,19]. Conclusions: Our results suggest an association between NKG2D polymorphisms and the risk of cutaneous malignant melanoma
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