The GSTT1 polymorphism of the glutathione S-transferase system in the intratumoral microvessel density of breast cancer patients
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It is well established that hypoxic microenvironment contributes to breast cancer progression by activation of transcriptional genes that promote angiogenesis. By promoting the antioxidant activity of glutathione, glutathione S-transferases (GSTs) are likely to facilitate the hypoxia-inducible factor-1α (HIF-1α) activity, therefore stimulating the angiogenesis. We investigated herein the influence of the GSTM1 and GSTT1 polymorphisms in the intratumoral angiogenesis of 87 patients with sporadic breast cancer. The intratumoral microvessel density (IMVD) of formalin-fixed paraffin-embedded tissues samples from all patients was determined by immunohistochemistry. The high IMVD was defined as a median microvessel counting higher than 18.7 after the analysis of histogram with all the results. The high IMVD was more common in patients with the GSTT1 wild genotype than in those with the GSTT1 null genotype (P = 0.04). Our results suggest, for the first time, that the GSTT1 polymorphism constitutes an inherited determinant of intratumoral angiogenesis in sporadic breast cancer.
KeywordsGSTM1 GSTT1 Angiogenesis Breast cancer
This work was supported by Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP).
Conflicts of interests
The authors declare that they have no competing interests.
G.J.L. and C.S.P.L. conceived and participated in all steps of the study. G.A.P. performed and processed the immunohistochemical experiments. A.A.S. and J.V. participated in the analysis of immunohistochemical data, in statistical analysis and discussion of the results. C.C.F. and M.S.C.G. performed the clinical evaluation of the patients. All authors read and approved the final version of the manuscript.
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