Deficient DNA repair capacity associated with increased risk of breast cancer

Deficiencies in the ability of cells to repair damaged DNA are associated with an increased risk of breast cancer, according to a new study in the January 19 issue of the Journal of the National Cancer Institute.

DNA repair is the system of defenses designed to protect the integrity of the genome. Studies have suggested that deficiency in cells’ capacity for DNA repair contributes to the accumulation of DNA damage and accelerates the genetic changes involved in carcinogenesis.

To evaluate whether reduced DNA repair capacity in the nucleotide excision pathway that fixes DNA alterations known as bulky DNA adducts is associated with breast cancer risk, Regina M. Santella, Ph.D., of the Columbia University Mailman School of Public Health in New York, and colleagues analyzed cell lines generated from blood samples taken from pairs of sisters in which one sister had been diagnosed with breast cancer and the other had not.

They found that DNA repair capacity was lower in breast cancer patients than in the control subjects. Deficient DNA repair capacity was associated with a twofold increase in the risk of breast cancer. In addition, when the data were stratified into quartiles of DNA repair capacity, the risk of breast cancer was three times higher among women with the poorest DNA repair capacity compared with those with the highest.

“[T]hese data support the hypothesis that deficient DNA repair capacity is associated with susceptibility to breast cancer and may be a valuable in vitro biomarker to identify high-risk subjects, especially in familial breast cancer families,” the authors write. “It is unclear at this time whether there are any interventions that could alter DNA repair capacity and what effect such interventions might have on risk.”

In an editorial, Marianne Berwick, Ph.D., M.P.H., of the University of New Mexico in Albuquerque, and Paolo Vineis, M.D., M.P.H., of Imperial College in London and the University of Torino in Italy, discuss the difficulties in designing studies of DNA repair capacity and the need for the development of better laboratory tests for such studies. “When DNA repair capacity can be measured easily and quickly, the scientific community will be able to clearly understand the role of DNA repair capacity in the development of cancer and possibly to develop interventions to reduce cancer incidence and mortality,” they write.