Glutathione S-transferase GSTIM1 and GSTT1 genotypes in ovarian cancer: association with p53 expression and survival

The objective of this study was to determine whether the association betwee n GSTM1 null/GSTTI null and survival in ovarian cancer is mediated by the i nfluence of these genes on p53 expression. In 81 women with pure invasive o varian cancer, GSTM1 null and GSTT1 null genotypes were identified using po lymerase chain reaction and p53 expression was assessed using immunohistoch emistry. The association of these factors with survival was examined using Cox's proportional hazards regression models. Performance status (P < 0.001), operative stage (P = 0.004), residual disea se (P = 0.001), histologic subtype (P = 0.05), tumor grade (P = 0.007), and the combined GSTMI null/GSTT1 null genotype (P = 0.023) were all individua lly associated with survival. p53 expression was not associated with surviv al (P = 0.45). In a multivariate analysis, the effects of GSTM1 null/GSTT1 null on survival were lost when residual disease and tumor grade were inclu ded. The effects of p53 expression on survival were unchanged when residual disease, tumor grade, operative stage, and performance score were included . GSTM1 null/GSTT1null did not influence the effects of p53 expression on s urvival and vice versa. The GSTM1 null/GSTT1 null genotype was associated w ith response to primary chemotherapy (P = 0.007) but p53 expression was not . We conclude that the association of GSTM1 null/GSTT1 null with survival a ppears to be mediated through different mechanisms to p53 expression in ova rian cancer and in addition, map be a better predictor of outcome.