Genetic regulation of ionizing radiation sensitivity and breast cancer risk

Environ Mol Mutagen. 2002;39(2-3):208-15. doi: 10.1002/em.10058.


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; P(trend) = 0.002). In controls, prolonged cell-cycle delay was significantly associated with the number of variant alleles in APE1 Asp148Glu and XRCC1 Arg399Gln genotypes (P(trend) = 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Substitution
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Carbon-Oxygen Lyases / genetics*
  • Case-Control Studies
  • DNA Repair / genetics
  • DNA, Neoplasm / genetics*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • DNA-Binding Proteins / genetics*
  • Female
  • G2 Phase / genetics
  • G2 Phase / radiation effects
  • Genotype
  • Humans
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Radiation Tolerance / genetics*
  • Risk Assessment
  • X-ray Repair Cross Complementing Protein 1


  • DNA, Neoplasm
  • DNA-Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • X-ray repair cross complementing protein 3
  • XRCC1 protein, human
  • Carbon-Oxygen Lyases
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase