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Br J Dermatol. 2019 Mar 1. doi: 10.1111/bjd.17833. [Epub ahead of print]

High naevus count and MC1R red hair alleles contribute synergistically to increased melanoma risk.

Author information

1
Dermatology Research Centre, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
2
QIMR Berghofer Medical Research Institute, Brisbane, Australia.
3
Department of Dermatology, University Medical Center, Tübingen, Germany.
4
Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia.

Abstract

BACKGROUND:

A high total body naevus count is the highest risk factor for melanoma; the red hair colour phenotype of red hair, freckling and pale skin that burns easily, produced by MC1R R alleles, also predisposes to melanoma.

OBJECTIVE:

To determine whether the known melanoma risk factors of high naevus count and red hair or MC1R R alleles act synergistically to increase melanoma risk.

METHODS:

The Brisbane Naevus Morphology Study drew 1267 participants from volunteers presenting at a melanoma unit, dermatology outpatient clinic, private dermatology clinics, Brisbane Longitudinal Twin Study and QSkin study. We examined pigmentation characteristics, total body naevus ≥5mm count, and MC1R, ASIP and CDKN2A genotype in participants with and without a personal history of melanoma, living in the very high incident UV setting of Queensland, Australia.

RESULTS:

Cases were older than controls (median 57 vs 33 years). Compared to individuals with dark brown hair and 0-4 naevi, individuals with red hair and 20+ naevi had a melanoma OR 10·0 (95%CI 4·2-24·3). Individuals with MC1R R/R genotype and 20+ naevi ≥5mm had a melanoma OR 25·1 (95%CI 8·4-82·7) compared to WT/WT individuals with 0-4 naevi. The highest risk group, Australian men with MC1R R/R genotype and 20+ moles, had an absolute risk of melanoma to age 75 of 23·3%, compared to 0·8% for men with WT/WT genotype and 0-4 naevi.

CONCLUSIONS:

Patients living in a high incident UV setting with many large naevi and the red hair colour phenotype, particularly those with MC1R R/R genotype, have a high risk of melanoma above the threshold recommended for screening in other cancers and should undergo intensive physician-led surveillance. This article is protected by copyright. All rights reserved.

KEYWORDS:

MC1R ; RHC phenotype; melanocortin-1 receptor; melanoma; naevi; pigmentation

PMID:
30820946
DOI:
10.1111/bjd.17833

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