Inherited variants in the MC1R gene and survival from cutaneous melanoma: a BioGenoMEL study

• Published in: Pigment cell and melanoma research Vol. 25; no. 3; pp. 384 - 394
• Main Authors: Davies, John R., Randerson-Moor, Juliette, Kukalizch, Kairen, Harland, Mark, Kumar, Rajiv, Madhusudan, Srinivasan, Nagore, Eduardo, Hansson, Johan, Höiom, Veronica, Ghiorzo, Paola, Gruis, Nelleke A., Kanetsky, Peter A., Wendt, Judith, Pjanova, Dace, Puig, Susana, Saiag, Philippe, Schadendorf, Dirk, Soufir, Nadem, Okamoto, Ichiro, Affleck, Paul, García-Casado, Zaida, Ogbah, Zighereda, Ozola, Aija, Queirolo, Paola, Sucker, Antje, Barrett, Jennifer H., van Doorn, Remco, Bishop, D. Timothy, Newton-Bishop, Julia
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2012
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Cohort Studies; Female; Follow-Up Studies; forest plot; Genetic Predisposition to Disease; Genetic Variation; Hair Color - genetics; Humans; Inheritance Patterns - genetics; Male; MC1R; Medicin och hälsovetenskap; melanoma; Melanoma - genetics; Melanoma - mortality; Middle Aged; MITF; Prevention & Epidemiology; Receptor, Melanocortin, Type 1 - genetics; Skin Neoplasms - genetics; Skin Neoplasms - mortality; Survival Analysis; Young Adult
• ISSN: 1755-1471; 1755-148X; 1755-148X
• DOI: 10.1111/j.1755-148X.2012.00982.x

Summary Inherited MC1R variants modulate MITF transcription factor signaling, which in turn affects tumor cell proliferation, apoptosis, and DNA repair. The aim of this BioGenoMEL collaborative study in 10 melanoma cohorts was to test the hypothesis that inherited variants thereby moderate survival expectation. A survival analysis in the largest cohort (Leeds) was carried out adjusting for factors known to impact on survival. The results were then compared with data from nine smaller cohorts. The absence of any consensus MC1R alleles was associated with a significantly lower risk of death in the Leeds set (HR, 0.64; 95% CI, 0.46–0.89) and overall in the 10 data sets (HR, 0.78; 95% CI, 0.65–0.94) with some support from the nine smaller data sets considered together (HR, 0.83; 95% CI, 0.67–1.04). The data are suggestive of a survival benefit for inherited MC1R variants in melanoma patients.