DNA repair capacity as a possible biomarker of breast cancer risk in female BRCA1 mutation carriers.
The BRCA1 gene product helps to maintain genomic integrity through its participation in the cellular response to DNA damage: specifically, the repair of double-stranded DNA breaks. An impaired cellular response to DNA damage is a plausible mechanism whereby BRCA1 mutation carriers are at increased risk of breast cancer. Hence, an individual's capacity to repair DNA may serve as a useful biomarker of breast cancer risk. The overall aim of the current study was to identify a biomarker of DNA repair capacity that could distinguish between BRCA1 mutation carriers and non-carriers. DNA repair capacity was assessed using three validated assays: the single-cell alkaline gel electrophoresis (comet) assay, the micronucleus test, and the enumeration of gamma-H2AX nuclear foci. DNA repair capacity of peripheral blood lymphocytes from 25 cancer-free female heterozygous BRCA1 mutation carriers and 25 non-carrier controls was assessed at baseline and following cell exposure to gamma-irradiation (2 Gy). We found no significant differences in the mean tail moment, in the number of micronuclei or in the number of gamma-H2AX nuclear foci between the carriers and non-carriers at baseline, and following gamma-irradiation. These data suggest that these assays are not likely to be useful in the identification of women at a high risk for breast cancer.
Kotsopoulos
J
J
Centre for Research in Women's Health, Women's College Hospital, 790 Bay Street, Room 750, 7th Floor, Toronto, Ontario, Canada.
Chen
Z
Z
Vallis
K A
KA
Poll
A
A
Ainsworth
P
P
Narod
S A
SA
D000328:Adult; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D020552:Comet Assay / Q000379:methods; D004247:DNA / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D005720:Gamma Rays; D019398:Genes, BRCA1; D006657:Histones / Q000737:chemistry / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000378:metabolism* / Q000528:radiation effects; D015162:Micronucleus Tests; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012984:Software; D013194:Staining and Labeling; D013223:Statistics as Topic / Q000379:methods; D011795:Surveys and Questionnaires
D014408:Biomarkers, Tumor; C468783:H2AX protein, human; D006657:Histones; D004247:DNA