Repair of DNA Damage Differs Between Sisters With and Without Breast Cancer

Regina M. Santella, Ph.D.
Columbia University
P30ES09089

Background: As is the case for many types of cancer, breast cancer results from complex interactions of genes and environmental exposures. Individuals differ in both their unique genetic makeup and the exposures that they encounter throughout their lifetimes. Damage to DNA is known to be a critical early step in the development of cancer since unrepaired damage leads to alterations in cellular functions. Therefore, individual differences in DNA repair capacity may influence the risk of developing cancer.

To test this hypothesis, NIEHS-supported researchers at Columbia University in New York evaluated the DNA repair capacity in breast cancer patients by analyzing sister pairs—one with breast cancer and one without. Cell culture lines for 158 breast cancer patients and 154 control sisters were obtained from the Metropolitan New York Registry of Breast Cancer Families. The cell cultures were treated with a DNA damaging agent (benzo[a]pyrene diolepoxide) followed by a standard DNA repair assay known as nucleotide excision repair to determine the extent of the damage and repair capacity.

Advance: DNA repair capacity of breast cancer patients proved to be statistically lower than that of their sisters without breast cancer. This difference translated into a two-fold increase in the risk for developing breast cancer. Additional data analyses, which divided DNA repair capacity into quartiles, resulted in a dose-dependent association between deficient DNA repair capacity and breast cancer risk. Using the quartile with the highest repair capacity as the control group, the risk of breast cancer development increased from 1.23 to 2.38 to 2.99 in a statistically significant trend analysis.

Implications: This study supports the theory that deficits in DNA repair capacity are associated with higher susceptibility of breast cancer development. The finding may become a valuable marker to identify women who are at high risk for the disease, especially among families with high incidence of breast cancer. Further research is necessary to determine if therapeutic interventions could improve DNA repair capacity. In the meantime, avoiding the environmental exposures that lead to DNA damage, such as exposure to the sun, smoking, and chemical agents, could reduce the risk of cancer in repair deficient women.

Citation: Kennedy DO, Agrawal M, Shen J, Terry MB, Zhang FF, Senie RT, Motykiewicz G, Santella RM. DNA repair capacity of lymphoblastoid cell lines from sisters discordant for breast cancer. J Natl Cancer Inst. 2005 Jan 19;97(2):127-32.