Journal of dermatological science · 2008
The D84E variant of the alpha-MSH receptor 1 gene is associated with cutaneous malignant melanoma early onset.
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F-de-Misa Ricardo, Hernández-Jimenez José Gerardo, Carretero Hernández Gregorio, Pérez-Méndez Lina, Aguirre-Jaime Armando, Flores Carlos, Suárez Hernández José, Perera Molinero Antonio, Claveríe-Martín Félix
Аннотация
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.
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.