Influência dos polimorfismos P53 ARG72PRO, MDM2 T309G, BCL2 C(-938)A e BAX G(-248)A, relacionados com apoptose celular, na susceptibilidade ao melanoma cutâneo = : Influence of the polymorphisms P53 ARG72PRO, MDM2 T309G, BCL2 C (-938) A and BAX G (-248) A, involved with cellular apoptosis, incutaneous melanoma susceptibility / Influence of the polymorphisms P53 ARG72PRO, MDM2 T309G, BCL2 C (-938) A and BAX G (-248) A, involved with cellular apoptosis, incutaneous melanoma susceptibility

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

12/06/2012

RESUMO

The P53 and BAX (proapoptotic) and MDM2 and BCL2 (antiapoptotic) genes remove cells damaged by ultraviolet (UV) rays of the sunlight and, therefore, are related to the cutaneous melanoma (CM) origin. The Arg wild allele of the P53 Arg72Pro polymorphism is more efficient in inducing apoptosis than the variant Pro allele. The variant G and A alleles of the MDM2 T309G and BCL2 C(-948)A polymorphisms, and the A allele of the BAX G(-248) A polymorphism are related to higher and lower expressions of the encoded proteins, respectively, than the wild T, C and G wild alleles. Since the roles of the referred genetic polymorphisms on the risk and clinical manifestation of the tumor are still unclear, these were the main aims of the present study. Genomic DNA from 150 patients with CM and 150 controls was analyzed by polymerase chain reaction and enzymatic digestion. The frequencies of the P53 ArgArg and the BCL2 AA genotypes were higher in patients than in controls (58.7% versus 44.7%, P= 0.02) and (28.0% versus 15.3%, P= 0.004) respectively. Carriers of these genotypes had a 1.86 and 2.87-fold increased risks for MC than others, respectively. Excesses of the P53 ArgArg + BCL2 AA and P53 ArgArg + BAX AA were seen in patients when compared to controls (36.1% versus 16.9%, P= 0.002) and (29.5% versus 15.3%, P= 0.008), and carriers of these genotypes had a 3.43 and 2.71-fold increased risks for CM than others, respectively. We concluded that the P53 Arg72Pro, BCL2 C(-938)A and BAX G(-248)A polymorphisms alter the risk for CM in our sample. We believe that carriers of the ArgArg wild genotype and the variant AA genotypes of the respective genetic polymorphisms should receive additional recommendation to avoid exposition to sunlight and should be frequently evaluated by a dermatologist with the purpose of preventing and performing an early diagnosis of the disease, respectively.

ASSUNTO(S)

melanoma pele - câncer polimorfismo apoptose risco melanoma skin polymorphism apoptosis risk

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