The GSTT1 genotype is associated with p53 mutation status of breast cancer tumours

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The role of the glutathione S-transferases is to provide protection against reactive mutagenic electrophiles by catalysing their conjugation to glutathione. In humans there are four classes of cytosolic GSTs, α (GSTA), μ (GSTM), π (GSTP) and θ (GSTT). Homozygous deletions of 50% and 20% of the genes coding for GSTM1 and GSTT1, respectively, results in conjugation deficiency. An A-G polymorphism at nucleotide 313 results in an amino acid substitution (Ile105Val) in the substrate binding site of the GSTP1 gene. The risk to the individual carrying a variant of one of these genes is estimated to be low, but the high frequency in the population of some of these variants makes the population attributable risk high. The aim of this study is to investigate whether any associations exist between the above mentioned GST genotypes and breast cancer, and whether they affect the p53 mutation status of the tumours and penetrance of germline mutations in the BRCA2 gene. The polymorphisms have been analysed by PCR, electrophoresis and RFLP. No significant differences have been observed between the GST genotypes in the 258 controls and 450 cases analysed so far. Both groups will be enlarged to increase the power of the study. p53 mutations in breast cancer tumours are significantly increased in individuals carrying the GSTT1 null genotype, both alone and in combination with the GSTP1 AG/GG genotype. The effect of the GST genotypes on the penetrance of BRCA2 has to be studied further.