Methylation of Glutathione-S-Transferase P1 Promotor in Egyptian Females with Breast Cancer

Abstract

Background: Breast cancer (BC) is the second most common cancer after the lung cancer worldwide and number one killing cancer in Egyptian females . It is a multifactorial disease driven by different environmental, hormonal, genetic and epigenetic factors. Epigenetic alterations have been studied in cancer breast. Role of GSTP1 promotor methylation in breast cancer has been studied in different ethnic groups. Objectives: Current study aimed at studying the methylation status of the promotor region of glutathione-S-transferase P1 in breast ductal carcinoma of a cohort group of Egyptian females and its correlations with histopathological and prognostic parameters. Methods: Control group included 15 fresh normal breast tissues taken from BC female patients after leaving a clearly defined safety margin and a Patient group included confirmed 35 fresh breast ductal carcinoma tissue biopsies taken from female patients postoperatively. To all patients clinical examination, radiological examination (plain X-ray chest and or CT scan, ultrasonography of abdomen and pelvis were done), in addition to histopathological examination, typing, grading and staging of tumour, hormonal receptors status and molecular typing of breast mass. GSTP1 methylation status was evaluated using methyl specific polymerase chain reaction. Results: Statistical significant increase was found in methylation status of GSTP1 promotor gene in BC cases than that in control group, (60% of patients samples had methylated GSTP1 promotor vs only 6.7% of controls) (p= >0.001). No association was found between GSTP1 promotor methylation status and the poor prognostic factors neither with hormonal profile nor molecular type. However, GSTP1 promotor methylation were two times higher in postmenopausal than premenopausal cases and three times higher in late grade (III). Also GSTP1 promotor methylation was 2.4 times higher in Her2 positive cases than either ER or PR positive cases. Conclusion: Glutathione-S-Transferase P1 Promotor methylation plays a role in breast cancer development.