Distribution of MC1R Variants Among Melanoma Subtypes: P.R163Q is Associated with Lentigo Maligna Melanoma in a Mediterranean Population

Overview

Journal Br J Dermatol

Publisher Oxford University Press

Specialty Dermatology

Date 2013 May 8

PMID 23647022

Citations 10

Authors

J A Puig-Butille

C Carrera

R Kumar

Z Garcia-Casado

C Badenas

P Aguilera

J Malvehy

E Nagore

S Puig

Affiliations

Soon will be listed here.

Abstract

Background: Cutaneous melanoma tumour is classified into clinicohistopathological subtypes that may be associated with different genetic and host factors. Variation in the MC1R gene is one of the main factors of risk variation in sporadic melanoma. The relationship between MC1R variants and the risk of developing a specific subtype of melanoma has not been previously explored.

Objectives: To analyse whether certain MC1R variants are associated with particular melanoma subtypes with specific clinicohistopathological features.

Methods: An association study was performed between MC1R gene variants and clinicopathological subtypes of primary melanoma derived from 1679 patients.

Results: We detected 53 MC1R variants (11 synonymous and 42 nonsynonymous). Recurrent nonsynonymous variants were p.V60L (30·0%), p.V92M (11·7%), p.D294H (9·4%), p.R151C (8·8%), p.R160W (6·2%), p.R163Q (4·2%) p.R142H (3·3%), p.I155T (3·8%), p.V122M (1·5%) and p.D84E (1·0%). Melanoma subtypes showed differences in the total number of MC1R variants (P = 0·028) and the number of red hair colour variants (P = 0·035). Furthermore, an association between p.R163Q and lentigo maligna melanoma was detected under a dominant model of heritance (odds ratio 2·16, 95% confidence interval 1·07-4·37; P = 0·044). No association was found between p.R163Q and Fitzpatrick skin phototype, eye colour or skin colour, indicating that the association was independent of the role of MC1R in pigmentation. No association was observed between MC1R polymorphisms and other melanoma subtypes.

Conclusions: Our findings suggest that certain MC1R variants could increase melanoma risk due to their impact on pathways other than pigmentation, and may therefore be linked to specific melanoma subtypes.

Citing Articles

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Interest and Uptake of MC1R Testing for Melanoma Risk in a Diverse Primary Care Population: A Randomized Clinical Trial.

Hay J, Zielaskowski K, Meyer White K, Kaphingst K, Robers E, Guest D JAMA Dermatol. 2018; 154(6):684-693.

PMID: 29801061 PMC: 5999534. DOI: 10.1001/jamadermatol.2018.0592.

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