Influencia dos polimorfismos nos genes CYP1A1*2A, GSTM1, GSTT1 e GSTP1*B na susceptibilidade ao cancer de pulmão / Influence of the polymorphisms CYP1A1*2A, GSTM1, GSTT1 e GSTP1*B genes on lung cancer susceptibility

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

Cytochrome P-450 A1 (CYP1A1 ) is an important enzyme of carcinogen metabolism. Due to polymorphic regulation, CYP1A1 is a biomarker of genetic susceptibility to certain malignancies, especially lung cancer (LC). The first detected variation, named m1 or *2A, was a T-to-C transition in exon 7, with 1194bp, which produced a breakage point for the MspI enzyme. Originally, more Asians than Caucasians presented with LC. Intensive studies have shown that GSTM1, GSTT1 and GSTP1 genes are related to LC, which may lead to whole loss or certain hazard reduction. The GSTP1 Val/Val variant genotype has a strong activity, especially along with hydrocarbon diol epoxide and BPDE, leading to detoxification potency. The purpose of this study was to analyze the susceptibility of polymorphism genes to LC risk and the correlation of genotypes with clinical variations. In order to achieve these objectives, the genomic DNA of 200 patients with LC and 264 blood donors (controls) were analyzed through PCR and enzymatic digestion. Similar frequencies of homozygotic deletion of polymorphic isolated genes were observed in patients and controls, as follows: GSTM1 (45.5% vs 48.1%, p= 0.14), GSTT1 (13.5% vs 12.9%, p= 0.54), GSTM1/T1 both null (6.0% vs 4.9%, p= 0.83), GSTP1 gene Val/Val variant (12.5% vs 11.4%, p= 0.87) and the CYP1A1*2A variant (5.5% vs 3.4%, p= 0.69). The differences observed among the frequencies of all combined genotypes were not significant. The final results suggested that isolated and combined genotypes did not influence LC risk; on the other hand, there is a high susceptibility for LC in African-Brazilian people with CYP1A1*2A and GSTs hetero/variant genotype

ASSUNTO(S)

lung glutathiona transferase susceptibilidade a doença susceptibility polimorfismo (genetica) glutationa transferase pulmao - cancer polymorphisms

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