Association of TYR SNP rs1042602 with Melanoma Risk and Prognosis
Arrate Sevilla,
Ana Sánchez-Diez,
Sofía Cobo,
Neskuts Izagirre,
Conrado Martinez-Cadenas,
Rosa M. Martí,
Teresa Puértolas,
Blanca de Unamuno,
José Bañuls,
Rosa Izu,
Jesús Gardeazabal,
Aintzane Asumendi,
María D. Boyano,
Santos Alonso
Affiliations
Arrate Sevilla
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), 48940 Leioa, Spain
Ana Sánchez-Diez
Department of Dermatology, Basurto University Hospital, 48013 Bilbao, Spain
Sofía Cobo
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), 48940 Leioa, Spain
Neskuts Izagirre
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), 48940 Leioa, Spain
Conrado Martinez-Cadenas
Department of Medicine, Jaume I University of Castellon, 12071 Castellon, Spain
Rosa M. Martí
Department of Dermatology, Hospital Universitari Arnau de Vilanova, 25198 Lleida, Spain
Teresa Puértolas
Oncology Department, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
Blanca de Unamuno
Department of Dermatology, Hospital Universitario de La Fe, 46026 Valencia, Spain
José Bañuls
Dermatology Department, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), 03010 Alicante, Spain
Rosa Izu
Biocruces-Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Jesús Gardeazabal
Biocruces-Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Aintzane Asumendi
Biocruces-Bizkaia Health Research Institute, 48903 Barakaldo, Spain
María D. Boyano
Biocruces-Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Santos Alonso
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), 48940 Leioa, Spain
Cutaneous melanoma is the most aggressive of skin tumors. In order to discover new biomarkers that could help us improve prognostic prediction in melanoma patients, we have searched for germline DNA variants associated with melanoma progression. Thus, after exome sequencing of a set of melanoma patients and healthy control individuals, we identified rs1042602, an SNP within TYR, as a good candidate. After genotyping rs1042602 in 1025 patients and 773 healthy donors, we found that the rs1042602-A allele was significantly associated with susceptibility to melanoma (CATT test: p = 0.0035). Interestingly, we also observed significant differences between patients with good and bad prognosis (5 years of follow-up) (n = 664) (CATT test for all samples p = 0.0384 and for men alone p = 0.0054). Disease-free-survival (DFS) analyses also showed that patients with the A allele had shorter DFS periods. In men, the association remained significant even in a multivariate Cox Proportional-hazards model, which was adjusted for age at diagnosis, Breslow thickness, ulceration and melanoma subtype (HR 0.4; 95% confidence interval (CI) 0.20–0.83; p = 0.0139). Based on our results, we propose that rs1042602-A is a risk allele for melanoma, which also seems to be responsible for a poorer prognosis of the disease, particularly in men.
