DNA repair proficiency in breast cancer patients and their first-degree relatives.

Abstract

Defective DNA repair capacity as measured by enumerating chromatid aberrations induced in G2 phase by X-irradiation may explain increased risk of breast cancer among relatives of patients. In the present study, chromatid damage was determined in peripheral blood lymphocytes (PBL) following in vitro exposure to 50R X-irradiation in G2 phase from 14 breast cancer (BrCa) patients, 19 first-degree relatives (FDR) of BrCa patients and 17 control women who had no family history of cancer for the last 3 generations. Controls, BrCa patients and their FDR had comparable frequency of gaps and breaks when cells were arrested with Colcemid (30 min) after X-irradiation. A steep decline in chromatid damage was observed in cells of controls when arrested after 30, 90 and 120 min of X-irradiation. BrCa patients and their FDR showed higher frequencies of lymphocytic chromatid damage as compared to controls. Chromatid damage (95 gaps + breaks per 100 cells) observed among controls at 90 min post X-irradiation was considered as the optimal level of efficient DNA repair. Thirty-five percent of controls, 93% of BrCa patients and 79% of FDR showed sub-optimal DNA repair. Amongst the FDR, the likelihood of having suboptimal DNA repair was 7 times higher and the risk of developing breast cancer was 2.7 times higher as compared to controls. Moreover, in the BrCa patients, there was frequent involvement of chromosomes 1 and 2, and chromosomes of B, D and E groups, while in FDR, involvement of chromosome 2 and chromosomes of B, D and E groups was more frequent.