{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T03:24:11Z","timestamp":1793676251977,"version":"4.5.1"},"reference-count":45,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T00:00:00Z","timestamp":1553731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2032 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\u2014NK3 (CAT haplotype)\u2014was 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.<\/jats:p>","DOI":"10.3390\/cancers11040438","type":"journal-article","created":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T03:50:21Z","timestamp":1553831421000},"page":"438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["NKG2D Polymorphism in Melanoma Patients from Southeastern Spain"],"prefix":"10.3390","volume":"11","author":[{"given":"Lourdes","family":"Gimeno","sequence":"first","affiliation":[{"name":"Immunology Service, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), Instituto Murciano de Investigaci\u00f3n Biom\u00e9dica (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helios","family":"Mart\u00ednez-Banaclocha","sequence":"additional","affiliation":[{"name":"Inflammation and Experimental Surgery Unit, IMIB, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Victoria","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Health Sciences, Universidad Cat\u00f3lica de San Antonio de Murcia (UCAM), 30107 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2400-9213","authenticated-orcid":false,"given":"Jos\u00e9 Miguel","family":"Bolarin","sequence":"additional","affiliation":[{"name":"Immunology Service, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), Instituto Murciano de Investigaci\u00f3n Biom\u00e9dica (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"Immunology Section, Complejo Hospitalario Universitario de Albacete, 02006 Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"L\u00f3pez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Immunology Section, Hospital Universitario de Gran Canaria Doctor Negr\u00edn, 35010 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4207-0739","authenticated-orcid":false,"given":"M. Roc\u00edo","family":"L\u00f3pez-Alvarez","sequence":"additional","affiliation":[{"name":"Center for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Rosa","family":"Moya-Quiles","sequence":"additional","affiliation":[{"name":"Immunology Service, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), Instituto Murciano de Investigaci\u00f3n Biom\u00e9dica (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Muro","sequence":"additional","affiliation":[{"name":"Immunology Service, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), Instituto Murciano de Investigaci\u00f3n Biom\u00e9dica (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Francisco","family":"Frias-Iniesta","sequence":"additional","affiliation":[{"name":"Dermatology Service, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), Instituto Murciano de Investigaci\u00f3n Biom\u00e9dica (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Mart\u00ednez-Escribano","sequence":"additional","affiliation":[{"name":"Dermatology Service, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), Instituto Murciano de Investigaci\u00f3n Biom\u00e9dica (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Roc\u00edo","family":"Alvarez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Immunology Service, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), Instituto Murciano de Investigaci\u00f3n Biom\u00e9dica (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2472-5893","authenticated-orcid":false,"given":"Alfredo","family":"Minguela","sequence":"additional","affiliation":[{"name":"Immunology Service, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), Instituto Murciano de Investigaci\u00f3n Biom\u00e9dica (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Campillo","sequence":"additional","affiliation":[{"name":"Immunology Service, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), Instituto Murciano de Investigaci\u00f3n Biom\u00e9dica (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,28]]},"reference":[{"key":"ref_1","first-page":"1005","article-title":"Melanoma: Epidemiology, Risk Factors, Pathogenesis, Diagnosis and Classification","volume":"28","author":"Rastrelli","year":"2014","journal-title":"In Vivo"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.sder.2010.10.005","article-title":"Epidemiology of melanoma","volume":"29","author":"Rigel","year":"2010","journal-title":"Semin. 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