title: Differential expression of DNA repair genes in Hispanic women with breast cancer.
abstract: Previous studies have found a link between a low DNA repair capacity (DRC) level and increased risk for breast cancer (BC). A recent study by Matta et al. 2012 showed that women with BC have an average reduction of 60% in DRC compared to controls (P< 0.001). Using the same group of Hispanic women, we selected a subgroup of cases (n=35) and controls (n=2) who donated their tumors and normal tissue for performing molecular studies in order to 1) compare the expression of DNA repair genes in breast tissue between BC cases and controls without this disease, 2) assess the correlation between gene expression and DRC levels, 3) examine whether DRC levels are associated with tumor DNA repair gene expression profiling when women were stratified according to their hormone receptor status. DRC levels were measured in lymphocytes by means of a host-cell reactivation assay. Gene expression levels were measured in tumors by means of DNA microarray analysis. Twenty-one DNA repair genes were found to be differentially and significantly expressed in women with BC. Those candidate genes wereCHEK2, EME1 (MMS4L), ERCC3 (XPB), FANCM, H2AFX (H2AX), HMGB1, HUS1, MBD4, NEIL3, PCNA, RAD1, RAD23B, RAD51, RAD54B, RDM1 (RAD52B), SHFM1 (DSS1), TP1, UBE2N(UBC13)and XRCC5 (Ku80). Most DNA repair genes (n=18 or 82%) were overexpressed, ranging from 3.76-fold (RDM1) to 1.47-fold (XRCC5). Only 4 genes (18%) were underexpressed, ranging from 62% (SAPCD1) to 25% (RAD23B). Statistically significant positive correlations between DRC level and gene expression were found for theRAD51, FANCBandFANCAgenes. We discuss the clinical and translational significance of these findings. Our results support the usefulness of studying DNA repair as a measure of BC risk. This study also provides a list of candidate DNA repair genes that might be associated with dysregulation of DNA repair in breast cancer.
authors.affiliation: PonceSchool of Medicine and Health Sciences, Department of Pharmacology, Physiology, and Toxicology, Department of Surgery, Ponce, Puerto Rico.
authors.forename: Jaime
authors.initials: J
authors.lastname: Matta
authors.affiliation: PonceSchool of Medicine and Health Sciences, Department of Pharmacology, Physiology, and Toxicology, Department of Surgery, Ponce, Puerto Rico.
authors.forename: Luisa
authors.initials: L
authors.lastname: Morales
authors.affiliation: PonceSchool of Medicine and Health Sciences, Department of Biochemistry, Ponce, Puerto Rico.
authors.forename: Julie
authors.initials: J
authors.lastname: Dutil
authors.affiliation: Public Health Program, Ponce School of Medicine and Health Sciences, Ponce, Puerto Rico.
authors.forename: Manuel
authors.initials: M
authors.lastname: Bayona
authors.affiliation: Public Health Program, Ponce School of Medicine and Health Sciences, Ponce, Puerto Rico.
authors.forename: Carolina
authors.initials: C
authors.lastname: Alvarez
authors.affiliation: Public Health Program, Ponce School of Medicine and Health Sciences, Ponce, Puerto Rico.
authors.forename: Erick
authors.initials: E
authors.lastname: Suarez
keywords: Breast cancer tumors; DNA repair capacity; DNA repair genes; microarray