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Inherited variants in the MC1R gene and survival from cutaneous melanoma: a BioGenoMEL study.
Pigment Cell Melanoma Res. 2012 May; 25(3):384-94
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12 Jul 2012
Frank Meyskens
F1000 Public Health & Epidemiology
University of California, Irvine,
Irvine, CA, USA.
F1000 Public Health & Epidemiology
University of California, Irvine,
Irvine, CA, USA.
New Finding
DOI: 10.3410/f.717697953.793153061
Melanocortin 1 receptor (MC1R) variants are associated with red hair and melanin biosynthesis, and the 'R' or 'r' variants of MC1R exhibit strong and weak associations with red hair, respectively. This article is the first study generated by BioGenoMEL as a consortium pooling data across multiple co and...Continue reading
Melanocortin 1 receptor (MC1R) variants are associated with red hair and melanin biosynthesis, and the 'R' or 'r' variants of MC1R exhibit strong and weak associations with red hair, respectively. This article is the first study generated by BioGenoMEL as a consortium pooling data across multiple cohorts, and the data are suggestive of a survival benefit for inherited MC1R variants in melanoma patients. Their study on the Leeds cohort (1397 cases) showed that melanoma cases with black hair or brown hair had poorer outcomes compared with those with blond hair or red hair (p=0.02). Consistently, there was also a significant inverse association between log Breslow thickness and MC1R score (a classification system scored from 0-4 where R/R is the highest) for the Philadelphia data, even though in the overall analysis of all 10 cohorts this association was weak and not statistically significant. To explain such observations, this study hypothesized that melanoma cells carrying MC1R variants exhibited deficient DNA repair capacity, resulting in apoptosis and better survival of patients.
Disclosures
None declared
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Meyskens F and Yang S: F1000Prime Recommendation of [Davies JR et al., Pigment Cell Melanoma Res 2012, 25(3):384-94]. In F1000Prime, 12 Jul 2012; DOI: 10.3410/f.717697953.793153061. F1000Prime.com/717697953#eval793153061
F1000Prime Recommendations, Dissents and Comments for [Davies JR et al., Pigment Cell Melanoma Res 2012, 25(3):384-94]. In F1000Prime, 19 May 2013; F1000Prime.com/717697953
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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.
© 2012 John Wiley & Sons A/S.
DOI: 10.1111/j.1755-148X.2012.00982.x
PMID: 22325793
