Abstract
SummaryInherited 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.
Highlights
Cutaneous melanoma is predominantly a cancer of white-skinned peoples, and those at increased risk include the very pale skinned (Gandini et al, 2005b), those with many melanocytic nevi (Gandini et al, 2005a), and those with a family history of melanoma (Gandini et al, 2005b)
The absence of any consensus melanocortin 1 receptor (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
Summary
Cutaneous melanoma is predominantly a cancer of white-skinned peoples, and those at increased risk include the very pale skinned (Gandini et al, 2005b), those with many melanocytic nevi (Gandini et al, 2005a), and those with a family history of melanoma (Gandini et al, 2005b). Both fair hair and blue eyes are associated with increased susceptibility (Gudbjartsson et al, 2008), the pigmentary phenotypes most strongly associated are freckling, red hair, and a tendency to burn in the sun. It was recognized many years ago that some inherited variants in the MC1R gene are associated with red hair, and these have been classified by Duffy et al (2004) into ‘R’ variants and ‘r’ variants, strongly and weakly associated with red hair, respectively
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