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DNA repair capacity of lymphoblastoid cell lines from sisters discordant for breast cancer.
J Natl Cancer Inst. 2005 Jan 19; 97(2):127-32.JNCI

Abstract

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.

Authors+Show Affiliations

Kennedy DO
Department of Environmental Health Sciences, Columbia University, New York, NY 10032, USA.
Agrawal M
No affiliation info available
Shen J
No affiliation info available
Terry MB
No affiliation info available
Zhang FF
No affiliation info available
Senie RT
No affiliation info available
Motykiewicz G
No affiliation info available
Santella RM
No affiliation info available

MeSH

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxideAnalysis of VarianceBreast NeoplasmsCarcinogensCase-Control StudiesDNA AdductsDNA DamageDNA RepairDNA, NeoplasmFemaleFluorescent Antibody Technique, DirectGenetic Predisposition to DiseaseHumansLogistic ModelsLymphocytesMutagensOdds RatioSiblings

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15657342

Citation

Kennedy, David O., et al. "DNA Repair Capacity of Lymphoblastoid Cell Lines From Sisters Discordant for Breast Cancer." Journal of the National Cancer Institute, vol. 97, no. 2, 2005, pp. 127-32.
Kennedy DO, Agrawal M, Shen J, et al. DNA repair capacity of lymphoblastoid cell lines from sisters discordant for breast cancer. J Natl Cancer Inst. 2005;97(2):127-32.
Kennedy, D. O., Agrawal, M., Shen, J., Terry, M. B., Zhang, F. F., Senie, R. T., Motykiewicz, G., & Santella, R. M. (2005). DNA repair capacity of lymphoblastoid cell lines from sisters discordant for breast cancer. Journal of the National Cancer Institute, 97(2), 127-32.
Kennedy DO, et al. DNA Repair Capacity of Lymphoblastoid Cell Lines From Sisters Discordant for Breast Cancer. J Natl Cancer Inst. 2005 Jan 19;97(2):127-32. PubMed PMID: 15657342.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DNA repair capacity of lymphoblastoid cell lines from sisters discordant for breast cancer. AU - Kennedy,David O, AU - Agrawal,Meenakshi, AU - Shen,Jing, AU - Terry,Mary Beth, AU - Zhang,Fang Fang, AU - Senie,Ruby T, AU - Motykiewicz,Grazyna, AU - Santella,Regina M, PY - 2005/1/20/pubmed PY - 2005/2/3/medline PY - 2005/1/20/entrez SP - 127 EP - 32 JF - Journal of the National Cancer Institute JO - J Natl Cancer Inst VL - 97 IS - 2 N2 - 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. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/15657342/DNA_repair_capacity_of_lymphoblastoid_cell_lines_from_sisters_discordant_for_breast_cancer_ DB - PRIME DP - Unbound Medicine ER -