Influence of p53 codon 72 exon 4, GSTM1, GSTT1 and GSTP1*B polymorphisms in lung cancer risk in a Brazilian population

Autor(es)

Honma, Helen N. ; De Capitani, Eduardo M. ; Perroud, Mauricio W., Jr. ; Barbeiro, Aristoteles S. ; Toro, Ivan F. C. ; Costa, Daniel B. ; Lima, Carmen S. P. ; Zambon, Lair

• Tipo de documento: Artigo Científico
• Fonte: LUNG CANCER; v. 61, n. 2, p. 11-pg., 2008-08-01.

Resumo

Purpose: Glutathione S-transferases (GST) modulates the effects of various cytotoxic and genotoxic agents, particularly those derived from benzo[a]pyrene, which is one of the main tobacco carcinogens. Both the mu 1 (GSTM1) and theta 1 (GSTT1) genes have a nut( variant allele in which the entire gene is absent. The GSTP1*B allele has an A to G transition at nucleotide 313 (codon 105) in exon 5, causing a change of isoleucine (lle) to valine (Val), which affects the electrophile binding site of GSTP1 and results in an enzyme with reduced activity. Polymorphisms in these metabolizing enzymes may alter the response to benzo[a]pirene-induced DNA damage. Polymorphisms in p53 may also modulate the risk of lung cancer (LC) carcinogenesis. Metabolism p53 codon 72 The aim of our study was to measure the frequency of GSTM1, GSTT1, GSTP1*B and p53 gene polymorphism; polymorphisms in a Brazilian population and determine the possible contribution of these genetic Polymorphism; variations to LC risk. Susceptibility; Patients and methods: Genomic DNA was obtained from 200 Brazilian patients with LC and 264 Xenobiotics blood donors (control group). All samples were analyzed by PCR and PCR-RFLP to determine GSTM1, GSTT1, GSTP1*B and p53 codon 72 genotypes. Multiple logistic regressions were used to adjust for confounding factors in this case-control study. Results: No statistical significance was observed between GSTM1, GSTT1 and GSTP1*B genetic polymorphisms, either isolated or combined, with LC incidence in the studied population. However, our data showed a higher frequency of p53 codon 72 A/P plus P/P genotype in African-Brazilian than Caucasian-Brazilian patients with LC, and we also found a higher frequency of the P/P genotype of the p53 gene in non-smokers compared to smokers with LC. Conclusions: Genetic polymorphisms of GST and p53 codon 72 did not increase the risk of LC in Brazilian patients. The A/P plus P/P genotype of p53 codon 72 is more common in LC patients with African ethnical background and the P/P genotype more prevalent in non-smoking related LC. (C) 2008 Elsevier Ireland Ltd. All rights reserved. (AU)

• Processo FAPESP: 04/13519-5 - Influência dos polimorfismos dos genes CYP1A1, GSTM1, GSTT1, GSTP1 e do gene P53 (códon 72) na susceptibilidade ao câncer de pulmão
• Beneficiário: Lair Zambon
• Modalidade de apoio: Auxílio à Pesquisa - Regular