SLC45A2: a novel malignant melanoma-associated gene

Authors

  • L.P. Fernandez,

    1. Human Genetics Group, Human Cancer Genetics Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain
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  • R.L. Milne,

    1. Spanish National Genotyping Centre, CeGen, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain
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  • G. Pita,

    1. Spanish National Genotyping Centre, CeGen, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain
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  • J.A. Avilés,

    1. Department of Dermatology, Gregorio Marañón General University Hospital, Madrid, Spain
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  • P. Lázaro,

    1. Department of Dermatology, Gregorio Marañón General University Hospital, Madrid, Spain
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  • J. Benítez,

    1. Human Genetics Group, Human Cancer Genetics Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain
    2. Spanish National Genotyping Centre, CeGen, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain
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  • G. Ribas

    Corresponding author
    1. Human Genetics Group, Human Cancer Genetics Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain
    • Human Genetics Group, Human Cancer Genetics Department, Centro Nacional de Investigaciones Oncológicas (CNIO), C/Melchor Fdz Almagro,3, E-28029 Madrid, Spain
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  • Communicated by Jacques S. Beckmann

Abstract

Human pigmentation appears to be one of the strongest risk factors for malignant melanoma (MM). In humans, there is a long list of genes known to be involved in rare pigmentary disorders such as albinism. These genes explain most of the variation in pigmentation phenotypes seen in human populations, and they do this by regulating the level of synthesis, chemical composition, packaging, and distribution of melanin. This Spanish case-control study included 131 consecutive melanoma patients and 245 control subjects frequency-matched for sex and age. A total of 23 SNPs in six candidate genes (ASP, OCA2, TYR, TYRP1, SILV, and SLC45A) belonging to the pigmentation pathway were genotyped. We found that the variant allele of c.1122C>G, p.Phe374Leu (NCBI dbSNP rs16891982) in SLC45A2 (membrane associated transporter previously known as MATP) was associated with protection from MM (OR, 0.41; 95% CI, 0.24–0.70; P=0.008 after adjustment for multiple testing). This association was validated by the consistent link observed with dark hair, dark skin, dark eye color, and the presence of solar lentigins and childhood sunburns. This is the first time SLC45A2 has been described as a melanoma susceptibility gene in a light-skinned population. Hum Mutat 0,1–7, 2008. © 2008 Wiley-Liss, Inc.

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