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 |
|---|---|
| Pages (from-to) | 208-215 |
| Number of pages | 8 |
| Journal | Environmental and Molecular Mutagenesis |
| Volume | 39 |
| Issue number | 2-3 |
| DOIs | |
| State | Published - Apr 9 2002 |
| Externally published | Yes |
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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
Cite this
Genetic regulation of ionizing radiation sensitivity and breast cancer risk. / Hu, Jennifer; Smith, Tasha R.; Miller, Mark Steven; Lohman, Kurt; Case, L. Douglas.
In: Environmental and Molecular Mutagenesis, Vol. 39, No. 2-3, 09.04.2002, p. 208-215.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetic regulation of ionizing radiation sensitivity and breast cancer risk
AU - Hu, Jennifer
AU - Smith, Tasha R.
AU - Miller, Mark Steven
AU - Lohman, Kurt
AU - Case, L. Douglas
PY - 2002/4/9
Y1 - 2002/4/9
N2 - 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.
AB - 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.
KW - Breast cancer risk
KW - Cell-cycle delay
KW - Genetic susceptibility
KW - Ionizing radiation
UR - http://www.scopus.com/inward/record.url?scp=0036203729&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036203729&partnerID=8YFLogxK
U2 - 10.1002/em.10058
DO - 10.1002/em.10058
M3 - Article
VL - 39
SP - 208
EP - 215
JO - Environmental and Molecular Mutagenesis
JF - Environmental and Molecular Mutagenesis
SN - 0893-6692
IS - 2-3
ER -