Get access

MC1R variation and melanoma risk in the Swedish population in relation to clinical and pathological parameters

Authors

  • Veronica Höiom,

    1.  Department of Oncology-Pathology, CCK, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
    Search for more papers by this author
    • *

      These authors contributed equally to this study.

  • Rainer Tuominen,

    1.  Department of Oncology-Pathology, CCK, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
    Search for more papers by this author
    • *

      These authors contributed equally to this study.

  • Max Käller,

    1.  Department of Gene Technology, School of Biotechnology, The Royal Institute of Technology (KTH), Stockholm, Sweden
    Search for more papers by this author
    • PRESENT ADDRESS Max Käller, LingVitae AB, Roslagstullsbacken 33, Stockholm, Sweden

  • Diana Lindén,

    1.  Department of Oncology-Pathology, CCK, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
    2.  Department of Oncology, Radiumhemmet, Karolinska University Hospital Solna, Stockholm, Sweden
    Search for more papers by this author
  • Afshin Ahmadian,

    1.  Department of Gene Technology, School of Biotechnology, The Royal Institute of Technology (KTH), Stockholm, Sweden
    Search for more papers by this author
  • Eva Månsson-Brahme,

    1.  Department of Oncology-Pathology, CCK, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
    2.  Department of Oncology, Radiumhemmet, Karolinska University Hospital Solna, Stockholm, Sweden
    Search for more papers by this author
  • Suzanne Egyhazi,

    1.  Department of Oncology-Pathology, CCK, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
    Search for more papers by this author
  • Klas Sjöberg,

    1.  Department of Medicine, Lund University, Malmö University Hospital, Malmö, Sweden
    Search for more papers by this author
  • Joakim Lundeberg,

    1.  Department of Gene Technology, School of Biotechnology, The Royal Institute of Technology (KTH), Stockholm, Sweden
    Search for more papers by this author
  • Johan Hansson

    1.  Department of Oncology-Pathology, CCK, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
    2.  Department of Oncology, Radiumhemmet, Karolinska University Hospital Solna, Stockholm, Sweden
    Search for more papers by this author

Veronica Höiom, e-mail: Veronica.Hoiom@ki.se

Summary

The genetic background of cutaneous malignant melanoma (CMM) includes both germ line aberrations in high-penetrance genes, like CDKN2A, and allelic variation in low-penetrance genes like the melanocortin-1 receptor gene, MC1R. Red-hair colour associated MC1R alleles (RHC) have been associated with red hair, fair skin and risk of CMM. We investigated MC1R and CDKN2A variation in relation to phenotype, clinical factors and CMM risk in the Swedish population. The study cohort consisted of sporadic primary melanoma patients, familial melanoma patients and a control group. An allele-dose dependent increase in melanoma risk for carriers of variant MC1R alleles (after adjusting for phenotype), with an elevated risk among familial CMM patients, was observed. This elevated risk was found to be significantly associated with an increased frequency of dysplastic nevi (DN) among familial patients compared to sporadic patients. MC1R variation was found to be less frequent among acral lentiginous melanomas (ALM) and dependent on tumour localisation. No association was found between CDKN2A gene variants and general melanoma risk. Two new variants in the POMC gene were identified in red haired individuals without RHC alleles.

Ancillary