Reduced DNA Repair Capacity in Breast Cancer Patients and Unaffected Individuals from Breast Cancer Families

Abstract

It has been suggested that increased fragile site expression in lymphocyte cultures can be used as a marker for genetic predisposition to cancer. We wished to determine whether aphidicolin (APC), an inhibitor of the DNA repair enzyme DNA polymerase α, could be used as a reliable biomarker in identification of DNA repair capacity in unaffected individuals at high risk from breast cancer families. PHA-stimulated lymphocyte cultures, with and without APC, were set up in 65 individuals, of whom 14 were breast cancer patients, 26 were unaffected individuals from breast cancer families, and 25 were controls. A significant proportion of breast cancer patients and unaffected individuals from familial breast cancer (FBC) families exhibited premature separation of centromeres (PSC) and aneuploidy in the untreated cultures. In the APC treated cultures, almost all such individuals exhibited a marked depression of mitotic index and increased aneuploidy, as compared to controls. Our results indicate that these individuals have defective DNA repair capacity. Such individuals could thus have a much higher risk of cancer as compared to persons exhibiting PSC and aneuploidy or DNA repair defects alone. We propose that APC may be a valuable biomarker in identifying individuals with genetic predisposition to cancer from FBC families.