The D84E variant of the alpha-MSH receptor 1 gene is associated with cutaneous malignant melanoma early onset.
J Dermatol Sci
; 52(3): 186-92, 2008 Dec.
Article
em En
| MEDLINE
| ID: mdl-18657399
ABSTRACT
BACKGROUND:
Alpha-melanocyte-stimulating hormone receptor 1 (MC1R) has an important role in skin pigmentation and variants of the gene have been established as independent risk factors for susceptibility to cutaneous malignant melanoma.OBJECTIVE:
To explore whether variants of the gene also influence the onset of the disease.METHODS:
We analyzed 285 melanoma patients of European ancestry for common variation in codon 84 (D84E) of the alpha-MSH receptor 1 gene, which is known to have functional consequences in MC1R protein activity.RESULTS:
The mean age difference at diagnosis between MC1R 84E carriers and non-carriers was 9 years (95% confidence interval [CI] 2-17; p=0.012), with 84E non-carrier patients being older. After adjusting for gender, Clark's level, phototype, eyes and hair colour, the risk for cutaneous malignant melanoma at any age was 2.07 times higher (95% CI 1.21-3.52; p=0.008) among MC1R 84E carriers. Enrolment criteria, geographical origin, Clark's levels and Breslow's indexes were similar between MC1R 84E carriers and non-carriers. Further analyses based on the Clark level and Breslow's index, both indicative for cancer invasion, reasonably supported an unbiased selection of patients during the study enrolment. Additional exon re-sequencing of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene in MC1R 84E carriers ruled out the presence of high penetrance mutations that have previously been associated with early onset of the disease.CONCLUSION:
Although our findings need to be confirmed by independent and larger studies we have described for the first time the association of D84E variant of the alpha-MSH receptor 1 gene as an independent risk factor for an earlier onset of cutaneous malignant melanoma.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Receptores do Hormônio Hipofisário
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Melanoma
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Dermatol Sci
Assunto da revista:
DERMATOLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Espanha