Skin colour and skin cancer - MC1R, the genetic link

Sturm, RA (2002) Skin colour and skin cancer - MC1R, the genetic link. Melanoma Research, 12 5: 405-416. doi:10.1097/00008390-200209000-00001

Author Sturm, RA
Title Skin colour and skin cancer - MC1R, the genetic link
Journal name Melanoma Research   Check publisher's open access policy
ISSN 0960-8931
Publication date 2002-01-01
Year available 2002
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1097/00008390-200209000-00001
Open Access Status Not yet assessed
Volume 12
Issue 5
Start page 405
End page 416
Total pages 12
Place of publication Philadelphia
Publisher Lippincott Williams & Wilkins
Language eng
Abstract Pigmentary traits such as red hair, fair skin, lack of tanning ability and propensity to freckle (the RHC phenotype) have been identified as genetic risk factors for both melanoma and non-melanocytic skin cancers when combined with the environmental risk factor of high ultraviolet light exposure. The human melanocortin-1 receptor (MC1R) is a key determinant of the pigmentation process and can account in large part for the diverse range of variation in human pigmentation phenotypes and skin phototypes. The MC1R coding sequence is highly polymorphic in human populations, with several of these variant forms of the receptor now known to be associated with the RHC phenotype. We have examined MC1R variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins with defined pigmentation characteristics. Variant allele frequencies have also been determined in several case-control studies of sporadic melanoma, basal cell carcinoma and squamous cell carcinoma, and in familial melanoma kindreds collected within Australia. These studies have shown that three RHC alleles; - Arg151Cys, Arg160Trp and Asp294His - were associated with increased risk in all forms of skin cancer and with penetrance and age of onset in familial melanoma in CDKN2A mutation carriers. There is a significant RHC allele heterozygote carrier effect on skin phototype and skin cancer risk, which indicates that variant MC1R alleles do not behave in a strictly recessive manner. Ultimately, the genetic and chemical assessment of melanin synthesis rather than skin colour will be the best indicator for skin cancer risk, and such genetic association studies combined with functional analysis of MC1R variant alleles should provide the link to understanding skin phototypes. (C) 2002 Lippincott Williams Wilkins.
Keyword Oncology
Medicine, Research & Experimental
basal cell carcinoma
melanoma genetics
solar keratosis
squamous cell carcinoma
Melanocyte-stimulating Hormone
Human Melanocortin-1 Receptor
Protein-coupled Receptors
Human Pigmentation Genes
Red Hair
Cutaneous Melanoma
Msh Receptor
Fair Skin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes This document is a journal review.

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 136 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 164 times in Scopus Article | Citations
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Created: Thu, 20 Sep 2007, 01:44:26 EST