BACKGROUND: Induction of DNA double strand breaks and alterations in the repair 
of these breaks is implicated in breast carcinogenesis. Prior studies have 
demonstrated that peripheral blood mononuclear cells (PBMC) from breast cancer 
patients exhibit increased numbers of DNA strand breaks after exposure to 
ionizing radiation, but these studies did not specifically measure DNA double 
strand breaks and it is not known whether chemical carcinogens produce similar 
effects.
MATERIALS AND METHODS: PBMC from 32 women undergoing breast surgery were 
genotyped at nine loci of seven DNA repair genes. DNA double strand break repair 
was measured using the neutral comet assay after exposure to ionizing radiation 
(0.5 Gy) or bioactivated benzo[a]pyrene (B[a]P, 5 microM.
RESULTS: PBMC from breast cancer patients showed higher levels of residual DNA 
double strand breaks 30 min after exposure to radiation than PBMC from patients 
with benign breast disease (1.40 times baseline [95% confidence intervals [CI] 
1.29-1.51] versus 1.24 times baseline [95% CI 1.15-1.33], respectively, P = 
0.04). The response to B[a]P trended in the same direction, but did not reach 
statistical significance. The MGMT K178R variant genotype was associated with 
improved DNA double strand break repair in PBMC exposed to B[a]P.
CONCLUSIONS: Reduced repair of radiation-induced DNA double strand breaks in 
PBMC is a robust biomarker of breast cancer risk. Reduced DNA repair capacity 
may have a genetic component even in sporadic breast cancer.