Genomic instability in breast malignant tumors as related to the concentration of intracelular aluminium and to estrogen receptor status

Abstract

Introduction: This study protocol is related to other ongoing studies on the carcinogenesis of gynecological and breast malignancies. Evidence suggests that aluminium compounds may trigger mutagenic processes in breast tissues. These compounds can enter cells by food ingestion or dermic exposure to substances containing aluminium. After entering the tissues, aluminium compounds may mimic estrogen. High aluminium concentration and accumulation have been described in association to DNA alterations and genic abnormalities. There are no in vitro and in vivo studies examining the specific gene abnormalities caused by aluminium compounds in breast tumors. Objective: To determine the instability of genes C-MYC, CCND1 and ERBB2 in breast tumor tissues related to the presence of estrogen receptors and intracellular aluminium. Subjects and Methods: This will be a cross-sectional study, including samples from 150 subjects. The samples will be collected from women who underwent mastectomy, in the Gynaecological Oncology and Breast Pathology clinics of Unicamp. Tissue samples will be examined with routine pathological workup and fragments containing invasive carcinoma will be taken to determination of estrogen receptor, using immunohistochemistry, and for the quantification of intracellular aluminium with atomic absorption spectrophotometry. The genomic instability for the genes C-MYC, CCND1 and ERBB2 will be assessed with fluorescence in situ hybridization (FISH). Genomic instability of each gene will be examined with regards to the presence and quantity of intracellular aluminium. Significance levels of 5% will be used in statistical calculations (p<=0,05 and 95% CI).