Links between DNA double strand break repair and breast cancer: Accumulating evidence from both familial and nonfamilial cases

• Published in: Cancer letters Vol. 248; no. 1; pp. 1 - 17
• Main Authors: Ralhan, Ranju, Kaur, Jatinder, Kreienberg, Rolf, Wiesmüller, Lisa
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 08-04-2007; Elsevier Limited
• Subjects: Aging; Brca; Breast Cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; DNA Breaks, Double-Stranded; DNA damage; DNA repair; DNA Repair - genetics; Double strand break; Family Health; Female; Genetic Predisposition to Disease; Hematology, Oncology and Palliative Medicine; Humans; Kinases; Models, Biological; Mutation; Polymorphism, Genetic; Recombination; Repair; Double strand break; Brca; Recombination; Repair; Breast Cancer
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2006.06.004

Abstract DNA double strand break (DSB) repair dysfunction increases the risk of familial and sporadic breast cancer. Advances in the understanding of genetic predisposition to breast cancer have also been made by screening naturally occurring polymorphisms. These studies revealed that subtle defects in DNA repair capacity arising from low-penetrance genes, or combinations thereof, are modified by other genetically determined or environmental risk factors and correlate to breast cancer risk. Overexpression of DSB repair enzymes, absence of surveillance factors and mutation or loss of heterozygosity in any of these genes contributes to the pathogenesis of sporadic breast cancers. The results identifying DSB repair defects as a common denominator for breast cancerogenesis focus attention on functional assays in order to assess DSB repair capacity as a diagnostic tool to detect increased breast cancer risk and to enable therapeutic strategies specifically targeting the tumor.