Premium
Inherited functional variants of the lymphocyte receptor CD5 influence melanoma survival
Author(s) -
Potrony Miriam,
Carreras Esther,
Aranda Fernando,
Zimmer Lisa,
PuigButille JoanAnton,
TellMartí Gemma,
Armiger Noelia,
Sucker Antje,
GiménezXavier Pol,
MartínezFlorensa Mario,
Carrera Cristina,
Malvehy Josep,
Schadendorf Dirk,
Puig Susana,
Lozano Francisco
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30184
Subject(s) - melanoma , immune system , single nucleotide polymorphism , immunology , haplotype , biology , medicine , oncology , cancer research , genotype , gene , genetics
Despite the recent progress in treatment options, malignant melanoma remains a deadly disease. Besides therapy, inherited factors might modulate clinical outcome, explaining in part widely varying survival rates. T‐cell effector function regulators on antitumor immune responses could also influence survival. CD5, a T‐cell receptor inhibitory molecule, contributes to the modulation of antimelanoma immune responses as deduced from genetically modified mouse models. The CD5 SNPs rs2241002 (NM_014207.3:c.671C > T, p.Pro224Leu) and rs2229177 (NM_014207.3:c.1412C > T, p.Ala471Val) constitute an ancestral haplotype (Pro224‐Ala471) that confers T‐cell hyper‐responsiveness and worsens clinical autoimmune outcome. The assessment of these SNPs on survival impact from two melanoma patient cohorts (Barcelona, N = 493 and Essen, N = 215) reveals that p.Ala471 correlates with a better outcome (OR= 0.57, 95% CI = 0.33–0.99, Adj. p = 0.043, in Barcelona OR = 0.63, 95% CI = 0.40–1.01, Adj. p = 0.051, in Essen). While, p.Leu224 was associated with increased melanoma‐associated mortality in both cohorts (OR = 1.87, 95% CI = 1.07–3.24, Adj. p = 0.030 in Barcelona and OR = 1.84, 95% CI = 1.04–3.26, Adj. p = 0.037, in Essen). Furthermore survival analyses showed that the Pro224‐Ala471 haplotype in homozygosis improved melanoma survival in the entire set of patients (HR = 0.27, 95% CI 0.11–0.67, Adj. p = 0.005). These findings highlight the relevance of genetic variability in immune‐related genes for clinical outcome in melanoma.