Genetic regulation of ionizing radiation sensitivity and breast cancer risk

Jennifer J. Hu, Tasha R. Smith, Mark Steven Miller, Kurt Lohman, L. Douglas Case

Research output: Contribution to journalArticle

105 Scopus citations

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 languageEnglish (US)
Pages (from-to)208-215
Number of pages8
JournalEnvironmental and Molecular Mutagenesis
Volume39
Issue number2-3
DOIs
StatePublished - Apr 9 2002
Externally publishedYes

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

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