8500 Expression of EGFR and HPV-associated p16 in head and neck cancer: correlation and influence on prognosis after radiotherapy in 1088 patients from the randomised DAHANCA 5,6&7 trials

Abstract

has also been involved in cell proliferation and apoptosis. We tested in this study whether the polymorphisms of the glutathione GSTM1, GSTT1 and GSTP1 might alter the risk for ovarian carcinoma (OC). Material and Methods: Genomic DNA from peripheral blood of 137 consecutive OC patients and 137 controls were analysed by the multiplexPCR for identification of the GSTM1 and GSTT1 genotypes and PCR-RFLP for identification of genotypes of the GSTP1. The differences between groups were analysed by c or Fisher exact test. Multivariate analysis served to obtain age and ethnic origin adjusted crude odds ratios (ORs). Results: Similar frequencies of the GSTM1 (37.6% versus 31.4%, P = 0.37) and GSTT1 (30.6% versus 24.8%, P = 0.25) null genotypes were seen in patients and controls. In contrast, the GSTP1 Ile/Ile genotype was more frequent in patients than in controls (59.1% versus 44.5%, P = 0.01). Individuals with this genotype had a 1.84 (95%CI: 1.14−3.01) fold increased risk for the disease. The frequency of the combined GSTM1 null and GSTP1 Ile/Ile genotypes was higher in patients than in controls (43.5% versus 24.6%; P = 0.02). Carriers of the genotype were under a 2.59 (95%CI: 1.18−5.64) fold increased risk for OC than others. Moreover, an excess of the GSTM1 null, GSTT1 null and GSTP1 Ile/Ile combined genotype was seen in patients compared to controls (30.3% versus 7.1%; P = 0.01). Individuals with the genotype had a 8.00 (95%CI: 1.77−35.87) fold increased risk for OC than carriers of the remaining genotypes. Conclusions: The results suggest that the variant GSTT1/GSTM1 null and GSTP1 Ile/Ile genotypes combination are linked to a substantial increased risk of development of OC. We hypothesised that GSTT1 and GSTM1 null genotypes leads to a loss of enzymatic conjugation activity, favouring the exposure of ovarian to estrogens. Apart from that, the GSTP1 Ile/Ile genotype may add OC risk through different effects on cell cycle by protecting cells against apoptosis promoting tumour cells survival. Financial support: FAPESP and CNPq.