Red Hair Variants of MC1R Influence Melanoma Risk Differently in Men, Women

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Individuals who are carriers of the red hair variants of MC1R are known to have an increased risk for melanoma.
Individuals who are carriers of the red hair variants of MC1R are known to have an increased risk for melanoma.

Red hair variants of MC1R contribute differently to pigmentation phenotype, and melanoma risk in men and women, according to the results of a hospital-based, case-control analysis conducted within the Molecular Markers of Melanoma (M3) Study program. Findings from the current analysis were published in JAMA Dermatology.

The investigators sought to explore the role of these variants in the risk for melanoma in men and women separately, since individuals who are carriers of the red hair variants of MC1R are known to have an increased risk for melanoma. Multivariate logistic regression analyses were performed to evaluate the effect of MC1R and melanoma risk in men vs women. The main study outcome was the association between MC1R variants and the risk for melanoma in men and women.

A total of 905 women (473 with melanoma, 432 controls) and 886 men (518 with melanoma, 368 controls) were included in the study. 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 (adjusted odds ratio [aOR] 2.19; 95% CI, 1.60-2.99; P <.001).

In contrast, in men only signs of actinic skin damage (ie, lentigines on the back [aOR 2.56; 95% CI, 1.47-4.45;  P =.001] and on the hands [aOR 2.31; 95% CI, 1.24-4.29;
P =.008]), as well as wrinkling on the neck (aOR 2.17; 95% CI, 1.23-3.82; P =.007) and sunburn (aOR 1.65; 95% CI, 1.12-2.42; P =.01) were significant risk factors for the development of melanoma.

The investigators concluded that because MC1R variants contribute in different ways to melanoma risk in men and women, this might prove helpful in improving 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 therapy.

Reference

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

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