Association of p53 genomic instability with the glutathione S-transferase null genotype in gastric cancer in the Portuguese population

Aims-p53 gene mutations are the most common genetic changes known to occur in human cancer. In previous studies, the presence of alterations to the p5 3 gene has been linked to the null phenotype of the glutathione S-transfera se mu gene (GSTM1). GSTM1 appears to be part of a protective mechanism agai nst the development of cancers in which environmental chemical carcinogens are involved. To screen for such an association in stomach cancer, p53 alle lic loss and genomic instability and GSTM1 genotypes were investigated in g astric tumour DNA samples from 113 patients. Methods-The polymerase chain (PCR) reaction was used to amplify a (CA) repe at array in the p53 locus; electrophoresis, genotyping, and allele quantifi cation were performed using an automated DNA sequencer and Genescan softwar e. The presence of the GSTM1 gene was determined by means of a differential PCR in which multiple genes were co-amplified in the same reaction tube. Results-Loss of heterozygosity (LOH) of the p53 gene was found in 36 of 87 informative cases and genomic instability was present in eight of 113 cases . Further analysis into histological subtypes and sites of tumours did not show any positive association with p53 loss. An association between the pre sence of LOH and the GSTM1 null genotype was not seen; however, all the sam ples with genomic instability of the p53 gene (eight of 113) also showed a GSTM1 null genotype. Conclusion-This study does not support the hypothesis of an association bet ween LOH in the p53 gene and the GSTM1 null genotype, but suggests that the GSTM1 null genotype might influence p53 genomic instability.