Abstract
Genetic variability in DNA repair may contribute to hypersensitivity to ionizing radiation (IR) and susceptibility to breast cancer. We used samples collected from a clinic-based breast cancer case-control study to test the working hypothesis that amino acid substitution variants of DNA repair genes may contribute to prolonged cell-cycle delay following IR and breast cancer risk. Fluorescence-activated cell sorter (FACS) analysis was used to measure cell-cycle delay. PCR-restriction fragment length polymorphism (RFLP) assays were used to determine four genotypes of three DNA repair genes: XRCC1, 194 Arg/Trp and 399 Arg/Gln; XRCC3, 241 Thr/Met; and APE1, 148 Asp/Glu. The data showed that breast cancer patients had a significantly higher delay index than that of controls (P < 0.001); the means ± SD for cases and controls were 36.0 ± 13.1 (n = 118) and 31.4 ± 11.5 (n = 225), respectively. There was a significant dose-response relationship between delay index, categorized into quartiles, and an increasing risk of breast cancer (crude odds ratios: 1.00, 1.00, 1.27, and 2.46, respectively; Ptrend = 0.002). In controls, prolonged cell-cycle delay was significantly associated with the number of variant alleles in APE1 Asp148Glu and XRCC1 Arg399Gln genotypes (Ptrend = 0.001). Although larger studies are needed to validate the results, our data suggest that an inherited hypersensitivity to IR may contribute to human breast carcinogenesis.
Original language | English (US) |
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Pages (from-to) | 208-215 |
Number of pages | 8 |
Journal | Environmental and Molecular Mutagenesis |
Volume | 39 |
Issue number | 2-3 |
DOIs | |
State | Published - 2002 |
Externally published | Yes |
Keywords
- Breast cancer risk
- Cell-cycle delay
- Genetic susceptibility
- Ionizing radiation
ASJC Scopus subject areas
- Environmental Science(all)
- Environmental Chemistry
- Genetics
- Genetics(clinical)
- Toxicology
- Health, Toxicology and Mutagenesis