X-Message-Number: 25654
Date: Tue, 1 Feb 2005 05:39:59 -0800 (PST)
From: Doug Skrecky <>
Subject: DNA repair and breast cancer

J Natl Cancer Inst. 2005 Jan 19;97(2):127-32
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.

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