Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with lentigo maligna melanoma in a Mediterranean population

Authors

  • J.A. Puig-Butillé,

    1. Centro Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
    2. Biochemical and Molecular Genetics Service, Department of Dermatology, Melanoma Unit, Hospital Clinic and IDIBAPS (Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer), Barcelona, Spain
    Search for more papers by this author
  • C. Carrera,

    1. Centro Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
    2. Department of Dermatology, Melanoma Unit, Hospital Clinic and IDIBAPS (Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer), Barcelona, Spain
    Search for more papers by this author
  • R. Kumar,

    1. Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany
    Search for more papers by this author
  • Z. Garcia-Casado,

    1. Department of Molecular Biology, Instituto Valenciano de Oncología, Valencia, Spain
    Search for more papers by this author
  • C. Badenas,

    1. Centro Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
    2. Biochemical and Molecular Genetics Service, Department of Dermatology, Melanoma Unit, Hospital Clinic and IDIBAPS (Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer), Barcelona, Spain
    Search for more papers by this author
  • P. Aguilera,

    1. Centro Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
    2. Department of Dermatology, Melanoma Unit, Hospital Clinic and IDIBAPS (Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer), Barcelona, Spain
    Search for more papers by this author
  • J. Malvehy,

    1. Centro Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
    2. Department of Dermatology, Melanoma Unit, Hospital Clinic and IDIBAPS (Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer), Barcelona, Spain
    Search for more papers by this author
  • E. Nagore,

    1. Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain
    Search for more papers by this author
  • S. Puig

    Corresponding author
    1. Department of Dermatology, Melanoma Unit, Hospital Clinic and IDIBAPS (Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer), Barcelona, Spain
    • Centro Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
    Search for more papers by this author

  • Funding sources The research at the Melanoma Unit in Barcelona was partially funded by Grants 03/0019, 05/0302, 06/0265 and 09/01393 from Fondo de Investigaciones Sanitarias, Spain; by the CIBER de Enfermedades Raras of the Instituto de Salud Carlos III, Spain; by the AGAUR 2009 SGR 1337 of the Catalan Government, Spain; by the European Commission under the 6th Framework Programme, contract no. LSHC-CT-2006-018702 (GenoMEL) and by the National Cancer Institute of the U.S. National Institutes of Health (CA83115). The work was carried out at the Esther Koplowitz Centre, Barcelona, Spain. The samples from the Instituto Valenciano de Oncología were collected from the Biobanco del Instituto Valenciano de Oncología.
  • Conflicts of interest None declared.

Correspondence

Susana Puig.

E-mails: susipuig@gmail.com; spuig@clinic.ub.es

Summary

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 (= 0·028) and the number of red hair colour variants (= 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; = 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.

Ancillary