Evaluation of PAX3 genetic variants and nevus number

Authors

  • Zighereda Ogbah,

    Corresponding author
    • Melanoma Unit, Department of Dermatology Hospital Clínic de Barcelona, IDIBAPS, Barcelona University, Barcelona, Spain
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  • Celia Badenas,

    1. Melanoma Unit, Biochemistry and Molecular Genetics Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona University, Barcelona, Spain
    2. Centre of Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain
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  • Mark Harland,

    1. Division of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine (LIMM), University of Leeds, Leeds, UK
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  • Joan A. Puig-Butille,

    1. Melanoma Unit, Biochemistry and Molecular Genetics Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona University, Barcelona, Spain
    2. Centre of Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain
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  • Fay Elliot,

    1. Division of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine (LIMM), University of Leeds, Leeds, UK
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  • Nuria Bonifaci,

    1. Breast Cancer and Systems Biology Unit, Translational Research Laboratory, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Spain
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  • Elisabet Guino,

    1. Biomarkers and Susceptibility Unit, Catalan Institute of Oncology, IDIBELL, L'Hospitalet, Barcelona, Spain
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  • Julie Randerson-Moor,

    1. Division of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine (LIMM), University of Leeds, Leeds, UK
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  • May Chan,

    1. Division of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine (LIMM), University of Leeds, Leeds, UK
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  • Mark M. Iles,

    1. Division of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine (LIMM), University of Leeds, Leeds, UK
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  • Daniel Glass,

    1. Department of Twin Research & Genetic Epidemiology, Kings College London, St. Thomas’ Hospital Campus, London, UK
    2. Department of Dermatology, The North West London Hospitals NHS Trust, London, UK
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  • Andrew A. Brown,

    1. Department of Twin Research & Genetic Epidemiology, Kings College London, St. Thomas’ Hospital Campus, London, UK
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  • Cristina Carrera,

    1. Melanoma Unit, Department of Dermatology Hospital Clínic de Barcelona, IDIBAPS, Barcelona University, Barcelona, Spain
    2. Centre of Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain
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  • Isabel Kolm,

    1. Melanoma Unit, Department of Dermatology Hospital Clínic de Barcelona, IDIBAPS, Barcelona University, Barcelona, Spain
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  • Veronique Bataille,

    1. Department of Twin Research & Genetic Epidemiology, Kings College London, St. Thomas’ Hospital Campus, London, UK
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  • Timothy D. Spector,

    1. Department of Twin Research & Genetic Epidemiology, Kings College London, St. Thomas’ Hospital Campus, London, UK
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  • Josep Malvehy,

    1. Melanoma Unit, Department of Dermatology Hospital Clínic de Barcelona, IDIBAPS, Barcelona University, Barcelona, Spain
    2. Centre of Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain
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  • Julia Newton-Bishop,

    1. Division of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine (LIMM), University of Leeds, Leeds, UK
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  • Miquel A. Pujana,

    1. Breast Cancer and Systems Biology Unit, Translational Research Laboratory, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Spain
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  • Tim Bishop,

    1. Division of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine (LIMM), University of Leeds, Leeds, UK
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  • Susana Puig

    Corresponding author
    1. Centre of Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain
    • Melanoma Unit, Department of Dermatology Hospital Clínic de Barcelona, IDIBAPS, Barcelona University, Barcelona, Spain
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CORRESPONDENCE Zighereda Ogbah, e-mail: zigheog@gmail.com

and Susana Puig, e-mails: susipuig@gmail.com; spuig@clinic.ub.es

Summary

The presence of a high nevus number is the strongest phenotypic predictor of melanoma risk. Here, we describe the results of a three-stage study directed at identifying risk variants for the high nevus phenotype. At the first stage, 263 melanoma cases from Barcelona were genotyped for 223 single-nucleotide polymorphisms (SNPs) in 39 candidate genes. Seven SNPs in the PAX3 gene were found to be significantly associated with nevus number under the additive model. Next, the associations for seven PAX3 variants were evaluated in 1217 melanoma cases and 475 controls from Leeds; and in 3054 healthy twins from TwinsUK. Associations with high nevus number were detected for rs6754024 (P values < 0.01) in the Barcelona and Leeds datasets and for rs2855268 (P values < 0.01) in the Barcelona and the TwinsUK sets. Associations (P values < 0.001) in the opposite direction were detected for rs7600206 and rs12995399 in the Barcelona and TwinsUK sets. This study suggests that SNPs in PAX3 are associated with nevus number, providing support for PAX3 as a candidate nevus gene. Further studies are needed to examine the role of PAX3 in melanoma susceptibility.

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