Epistatic interaction of Arg72Pro TP53 and -710 C/T VEGFR1 polymorphisms in breast cancer: predisposition and survival.
Mol Cell Biochem
; 379(1-2): 181-90, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23716179
ABSTRACT
The tumour-suppressor gene TP53 has been associated with the angiogenic pathway by a TP53 response element sequence of the VEGFR1 promoter. Within that sequence, the polymorphism -710 C/T VEGFR1, which confers variable transcriptional activation by TP53, has been identified. Our group found an association between this polymorphism and breast cancer (BC) risk. We decided to investigate a possible epistatic interaction between this polymorphism and others located at gene TP53. We chose four polymorphisms (Ex4 + 119G > C, IVS4-91A > G, IVS6 + 62A > G and IVS7 + 92T > G) to analyse out of a total of 461 controls and 453 BC patients in a Spanish population. The two-locus combined analysis of TP53 and -710 C/T VEGFR1 polymorphisms was performed with the multifactor dimension reduction approach. Kaplan-Meier disease-free survival curves were calculated using the SPSS package. Carriers of at least one Pro allele of the Ex4 + 119G > C TP53 polymorphism presented a significant BC risk [OR = 1.34, (95 % CI 1.03-1.75), p value = 0.029]. The epistatic gene-gene analysis showed that the best two-locus model was the combination between Ex4 + 119G > C TP53 and -710 C/T VEGFR1 showing OR of 1.44 (95 % CI 1.10-1.88, p value = 0.0083). Moreover, the Pro/Pro genotypes of Ex4 + 119G > C were associated with poor disease-free survival (p value = 0.013). We conclude that the Ex4 + 119G > C TP53 polymorphism is an independent, low penetrance marker of BC risk in this population. In addition, our findings suggest that the combination of Ex4 + 119G > C TP53 and -710 C/T VEGFR1 genotypes confers a higher risk to develop BC. Also, a possible association of the Ex4 + 119G > C TP53 genotype with decreased disease-free survival in these patients is proposed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Proteína Supressora de Tumor p53
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Polimorfismo de Nucleotídeo Único
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Receptor 1 de Fatores de Crescimento do Endotélio Vascular
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Epistasia Genética
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Espanha