Increased risk of developing cutaneous malignant melanoma is associated with variation in pigmentation genes and VDR, and may involve epistatic effects.
Melanoma Res
; 24(4): 388-96, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24926819
ABSTRACT
Cutaneous malignant melanoma (CMM) is a malicious human skin cancer that primarily affects individuals with light pigmentation and heavy sun exposure, but also has a known familial association. Multiple genes and polymorphisms have been reported as low-penetrance susceptibility loci for CMM. Here, we examined 33 candidate polymorphisms located in 11 pigmentation genes and the vitamin D receptor gene (VDR) in a population of 130 cutaneous melanoma patients and 707 healthy controls. The genotypes obtained were evaluated for main association effects and potential gene-gene interactions. MC1R, TYR, VDR and SLC45A2 genes were found to be associated with CMM in our population. The results obtained for major function MC1R mutations were the most significant [with odds ratio (OR)=1.787, confidence interval (CI)=1.320-2.419 and P=1.715(-4)], followed by TYR (rs1393350) (with OR=1.569, CI=1.162-2.118, P=0.003), VDR (GCCC haplotype in rs2238136-rs4516035-rs7139166-rs11568820 block) (with OR=5.653, CI=1.794-17.811, P=0.003) and SLC45A2 (rs16891982) (with OR=0.238, CI=0.057-0.987, P=0.048). The study also detected significant intermolecular epistatic effects between MC1R and TYR, SLC45A2 and VDR, HERC2 and VDR, OCA2 and TPCN2, as well as intramolecular interactions between variants within the genes MC1R and VDR. In the final multivariate logistic regression model for CMM development, only the gene-gene interactions discovered remained significant, showing that epistasis may be an important factor in the risk of melanoma.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Pigmentação da Pele
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Receptores de Calcitriol
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Melanoma
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Melanoma Res
Ano de publicação:
2014
Tipo de documento:
Article