Genetic regulation of ionizing radiation sensitivity and breast cancer risk

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

Research output: Contribution to journalArticle

101 Citations (Scopus)

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

Fingerprint

Radiation Tolerance
Ionizing radiation
Ionizing Radiation
cancer
Breast Neoplasms
repair
Repair
DNA Repair
Cells
DNA
genotype
Genes
Cell Cycle
Hypersensitivity
Genotype
gene
dose-response relationship
Polymorphism
Assays
Amino Acid Substitution

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 journalArticle

Hu, Jennifer ; Smith, Tasha R. ; Miller, Mark Steven ; Lohman, Kurt ; Case, L. Douglas. / Genetic regulation of ionizing radiation sensitivity and breast cancer risk. In: Environmental and Molecular Mutagenesis. 2002 ; Vol. 39, No. 2-3. pp. 208-215.
@article{2b9da0e68aab46968f808a8cf36bd44e,
title = "Genetic regulation of ionizing radiation sensitivity and breast cancer risk",
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.",
keywords = "Breast cancer risk, Cell-cycle delay, Genetic susceptibility, Ionizing radiation",
author = "Jennifer Hu and Smith, {Tasha R.} and Miller, {Mark Steven} and Kurt Lohman and Case, {L. Douglas}",
year = "2002",
month = "4",
day = "9",
doi = "10.1002/em.10058",
language = "English",
volume = "39",
pages = "208--215",
journal = "Environmental and Molecular Mutagenesis",
issn = "0893-6692",
publisher = "Wiley-Liss Inc.",
number = "2-3",

}

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 -