DNA repair capacity of lymphoblastoid cell lines from sisters discordant for breast cancer.
BACKGROUND
Interindividual differences in DNA repair capacity may influence cancer risk. We tested whether the nucleotide excision repair pathway was deficient in breast cancer case patients by analyzing sister pairs.


METHODS
Cell lines derived from sisters discordant for breast cancer (137 families containing 158 case patients and 154 control sisters) were obtained from the Metropolitan New York Registry of Breast Cancer Families. Lymphoblastoid cells were treated with benzo[a]pyrene diolepoxide (BPDE) for 30 minutes and were either harvested immediately or were washed and cultured in complete medium for 4 hours to allow DNA repair. Immunofluorescence using a polyclonal anti-BPDE-DNA primary antibody was used to quantify BPDE-DNA adducts. Percent DNA repair capacity was calculated from the difference between staining immediately after treatment minus that after 4 hours of repair, divided by the initial damage and was categorized into quartiles based on control values. Odds ratios and 95% confidence intervals (CIs) were calculated using conditional logistic regression models adjusted for age at blood donation, body mass index, and smoking. Statistical tests were two-sided.


RESULTS
Mean percent DNA repair capacity was lower in breast cancer case patients than in control subjects (difference = 8.6, 95% CI = 4.3 to 13.8, P = .001). Using the quartile with the highest percent DNA repair capacity as the referent group, adjusted odds ratios of breast cancer increased from 1.23 (95% CI = 0.57 to 2.65) to 2.38 (95% CI = 1.17 to 4.86) to 2.99 (95% CI = 1.45 to 6.17) (P(trend) = .002) as DNA repair capacity decreased.


CONCLUSIONS
Deficient DNA repair capacity is associated with increased breast cancer risk.
Kennedy
David O
DO
Department of Environmental Health Sciences, Columbia University, New York, NY 10032, USA.
Agrawal
Meenakshi
M
Shen
Jing
J
Terry
Mary Beth
MB
Zhang
Fang Fang
FF
Senie
Ruby T
RT
Motykiewicz
Grazyna
G
Santella
Regina M
RM
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000235:genetics*; D002273:Carcinogens; D016022:Case-Control Studies; D018736:DNA Adducts; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008214:Lymphocytes / Q000378:metabolism*; D009153:Mutagens; D016017:Odds Ratio; D035781:Siblings
D002273:Carcinogens; D018736:DNA Adducts; D004273:DNA, Neoplasm; D009153:Mutagens; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide