Influence of p53 codon 72 exon 4, GSTM1, GSTT1 and GSTP1*B polymorphisms in lung cancer risk in a Brazilian population.
OBJECTIVE
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 null 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 (Ile) 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. The aim of our study was to measure the frequency of GSTM1, GSTT1, GSTP1*B and p53 gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to LC risk.


METHODS
Genomic DNA was obtained from 200 Brazilian patients with LC and 264 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.
Honma
Helen N
HN
Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Distrito de Barão Geraldo, Campinas, São Paulo, Brazil.
De Capitani
Eduardo M
EM
Perroud
Maurício W
MW
Barbeiro
Aristóteles S
AS
Toro
Ivan F C
IF
Costa
Daniel B
DB
Lima
Carmen S P
CS
Zambon
Lair
L
D000368:Aged; D044383:Black People; D001938:Brazil / Q000453:epidemiology; D003062:Codon; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D044465:White People
D003062:Codon; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D016159:Tumor Suppressor Protein p53; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human