title: Tissue aluminum concentration does not affect the genomic stability of ERBB2, C-MYC, and CCND1 genes in breast cancer.
abstract: It has long been hypothesized that body tissue uptake of aluminum may have biological implications in breast cancer. In vitro and in vivo studies have shown that aluminum may trigger genomic instability by interfering with DNA strands. The objective of this study was to examine the relationship between aluminum concentrations in the peripheral and central areas of breast tumors with the instability of three key genes in breast cancer, ERBB2, C-MYC, and CCND1 and aneuploidy of the chromosomes harboring these genes. Tissue samples of 118 women treated for breast cancer were obtained. Evaluation of aluminum content was carried out using graphite furnace atomic absorption spectrometry. A tissue microarray slide containing the tumor samples was used in FISH assays to assess ERBB2, C-MYC, and CCND1 expressions as well as the statuses of their respective chromosomes 17, 8, and 11. Clinicopathological data were obtained from patient's records. Aluminum levels of >2.0 mg/kg were found in 20.3 and 22.1% of the central and peripheral breast tumor areas, respectively. Amplification and/or aneuploid-positive statuses for ERBB2/CEP17, C-MYC/CEP8, and CCND1/CEP11 were detected in 24, 36.7, and 29.3% of the tumors, respectively. We found that aluminum concentration was not related to these altered gene statuses. Our findings suggest that aluminum concentration does not affect genomic stability in breast tissues. Tissue microenvironment modifications, due to the presence of aluminum compounds, seem more appealing as a possible target for future studies to determine the implications of aluminum in breast carcinogenesis.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medical Sciences, State University of Campinas, Alexander Fleming, 101-Cidade Universitária Zeferino Vaz, Campinas, São Paulo, Brazil.
authors.forename: Raquel Mary
authors.initials: RM
authors.lastname: Rodrigues-Peres
authors.forename: Solange
authors.initials: S
authors.lastname: Cadore
authors.forename: Stefanny
authors.initials: S
authors.lastname: Febraio
authors.forename: Juliana Karina
authors.initials: JK
authors.lastname: Heinrich
authors.forename: Katia Piton
authors.initials: KP
authors.lastname: Serra
authors.forename: Sophie F M
authors.initials: SF
authors.lastname: Derchain
authors.forename: José
authors.initials: J
authors.lastname: Vassallo
authors.forename: Luis Otavio
authors.initials: LO
authors.lastname: Sarian
mesh_terms: D000328:Adult; D000535:Aluminum / Q000032:analysis*; D000782:Aneuploidy; D001940:Breast / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D042822:Genomic Instability; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D013054:Spectrophotometry, Atomic / Q000379:methods
chemical_list: D000535:Aluminum; D019938:Cyclin D1; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; C530104:CCND1 protein, human; C489427:MYC protein, human; C508053:ERBB2 protein, human