Derm Appeal Blog

Melanocortin 1 Receptor Variants as a Risk for Melanoma

Recently published findings in JAMA Dermatology explore the role of MC1R in melanoma risk, and whether it contributes differently to the skin cancer risk factors in males and females. MC1R, the melanocortin 1 receptor, is one of the key proteins involved in regulating mammalian skin and hair color: controlling the type of melanin being produced—and some MC1R gene variants have been previously investigated for their direct role in the pathogenesis of certain cancers.

The analysis is the result of a hospital-based, case-control analysis conducted within the Molecular Markers of Melanoma (M3) Study program, and results indicate that red hair variants of MC1R contribute differently to pigmentation phenotype, and melanoma risk in men and women. The investigators further sought to demonstrate the role of these variants in melanoma risk in both men and women separately, since carriers of the red hair variants of MC1R have a demonstrated increased risk for melanoma.

The primary study outcome was the association between MC1R variants and the risk for melanoma in men and women, conducted through multivariate logistic regression analyses. The study included a total of 905 women: 473 with melanoma, 432 controls—and 886 men: 518 with melanoma, 368 controls. The mean age of the participants was 59.2±15.6. In the women evaluated, carrying any MC1R red hair variant was an independent significant risk factor for melanoma; in contrast, only signs of actinic skin damage in men (i.e. lentigines on the back and on the hands, in addition to wrinkling on the neck and sunburn), were significant risk factors for the development of melanoma.

The investigators concluded that because MC1R variants contribute differently to melanoma risk in males and females, the findings could help improve the classification of risk factors according to gender, and should thus be considered in genetic counseling. Further investigation might eventually lead to sex-dependent prevention strategies, and appropriate therapies.

The 17th Annual South Beach Symposium will kick off its first day of education with a General Session on “Skin Cancer & Dermoscopy,” beginning with a lecture from Darrell S. Rigel, MD, MS on “Diagnosis, Management, and Treatment of Skin Cancer.”

SOURCES
L. Feller, R. A. G. Khammissa, B. Kramer, M. Altini, and J. Lemmer. Basal cell carcinoma, squamos cell carcinoma, and melanoma of the head and face [published online February 5, 2016]. Head & Face Medicine. https://doi.org/10.1186/s13005-016-0106-0

J. Wendt, C. Mueller, S. Rauscher, I. Fae, G. Fischer G, I. Okamoto. Contributions by MC1R variants to melanoma risk in males and females [published online June 13, 2018]. JAMA Dermatology. https://doi:10.1001/jamadermatol.2018.1252

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