BACKGROUND: Familial breast cancer is associated with mutations in several genes (BRCA1, BRCA2, p53, ATM) whose protein products protect against radiation-induced genotoxicity. This study tested whether sporadic breast cancer was associated with constitutive radiation hypersensitivity. METHODS: Blood lymphocytes and EBV-transformed lymphoblasts from patients with newly diagnosed breast cancer and controls without cancer were evaluated for ionizing radiation (IR)-induced chromosomal aberrations and cell cycle delays. Lymphoblasts from patients with ataxia telangiectasia (AT) and heterozygous AT carriers were tested as positive controls for radiation hypersensitivity. RESULTS: Lymphoblasts from AT patients and AT carriers displayed G2-irradiation, chromosomal hypersensitivity (GICH). Irradiated G2 phase lymphocytes from breast cancer cases and controls displayed 3-fold inter-individual variation in frequencies of chromatid damage. However, the percentage of breast cancer cases with damage frequencies in excess of 2 SD of the control mean (8/102 or 8%) was not significantly elevated compared to controls (2/48 or 4%, P=0.5). Lymphoblasts sampled 24 h after 3 Gy of IR also varied in the ratios of cells with 4N and 2N DNA content (4N/2N ratio), as a measure of cell cycle checkpoint function. 4N/2N ratios in irradiated lymphoblasts were strongly correlated with the fractions of S phase cells in un-irradiated control cultures (Pearson's correlation coefficient, r=0.87). After normalization to S fraction, the radiation-induced increment in the 4N/2N ratio was significantly elevated in AT lymphoblasts but not in lymphoblasts from AT carriers. The fraction of breast cancer cases with reduced checkpoint function (2/45 or 4%) was equal to the control fraction (2/45 or 4%). For breast cancer cases and controls, GICH in primary lymphocytes was not associated with reduced cell cycle checkpoint function in lymphoblasts. CONCLUSION: Constitutive radiation hypersensitivity in blood lymphocytes and lymphoblasts was not a useful biomarker for identifying women at increased risk of breast cancer.
BACKGROUND:Familial breast cancer is associated with mutations in several genes (BRCA1, BRCA2, p53, ATM) whose protein products protect against radiation-induced genotoxicity. This study tested whether sporadic breast cancer was associated with constitutive radiation hypersensitivity. METHODS: Blood lymphocytes and EBV-transformed lymphoblasts from patients with newly diagnosed breast cancer and controls without cancer were evaluated for ionizing radiation (IR)-induced chromosomal aberrations and cell cycle delays. Lymphoblasts from patients with ataxia telangiectasia (AT) and heterozygous AT carriers were tested as positive controls for radiation hypersensitivity. RESULTS: Lymphoblasts from AT patients and AT carriers displayed G2-irradiation, chromosomal hypersensitivity (GICH). Irradiated G2 phase lymphocytes from breast cancer cases and controls displayed 3-fold inter-individual variation in frequencies of chromatid damage. However, the percentage of breast cancer cases with damage frequencies in excess of 2 SD of the control mean (8/102 or 8%) was not significantly elevated compared to controls (2/48 or 4%, P=0.5). Lymphoblasts sampled 24 h after 3 Gy of IR also varied in the ratios of cells with 4N and 2N DNA content (4N/2N ratio), as a measure of cell cycle checkpoint function. 4N/2N ratios in irradiated lymphoblasts were strongly correlated with the fractions of S phase cells in un-irradiated control cultures (Pearson's correlation coefficient, r=0.87). After normalization to S fraction, the radiation-induced increment in the 4N/2N ratio was significantly elevated in AT lymphoblasts but not in lymphoblasts from AT carriers. The fraction of breast cancer cases with reduced checkpoint function (2/45 or 4%) was equal to the control fraction (2/45 or 4%). For breast cancer cases and controls, GICH in primary lymphocytes was not associated with reduced cell cycle checkpoint function in lymphoblasts. CONCLUSION: Constitutive radiation hypersensitivity in blood lymphocytes and lymphoblasts was not a useful biomarker for identifying women at increased risk of breast cancer.
Authors: Jiachun Lu; Qingyi Wei; Melissa L Bondy; Abenaa M Brewster; Therese B Bevers; Tse-Kuan Yu; Thomas A Buchholz; Funda Meric-Bernstam; Kelly K Hunt; S Eva Singletary; Li-E Wang Journal: Breast Cancer Res Treat Date: 2007-09-13 Impact factor: 4.872
Authors: Beth O Van Emburgh; Jennifer J Hu; Edward A Levine; Libyadda J Mosley; Nancy D Perrier; Rita I Freimanis; Glenn O Allen; Peter Rubin; Gary B Sherrill; Cindy S Shaw; Lisa A Carey; Lynda R Sawyer; Mark Steven Miller Journal: Oncol Rep Date: 2008-05 Impact factor: 3.906
Authors: Beth O Van Emburgh; Jennifer J Hu; Edward A Levine; Libyadda J Mosley; L Douglas Case; Hui-Yi Lin; Sommer N Knight; Nancy D Perrier; Peter Rubin; Gary B Sherrill; Cindy S Shaw; Lisa A Carey; Lynda R Sawyer; Glenn O Allen; Clara Milikowski; Mark C Willingham; Mark Steven Miller Journal: Mol Carcinog Date: 2008-02 Impact factor: 4.784
Authors: Liwen Zhang; Dennis A Simpson; Cynthia L Innes; Jeff Chou; Pierre R Bushel; Richard S Paules; William K Kaufmann; Tong Zhou Journal: Physiol Genomics Date: 2013-08-13 Impact factor: 3.107
Authors: Jeff W Hill; Kristina Tansavatdi; Kristin L Lockett; Glenn O Allen; Cristiane Takita; Alan Pollack; Jennifer J Hu Journal: Cancer Manag Res Date: 2009-04-30 Impact factor: 3.989
Authors: Farida S Akhtari; Tammy M Havener; Daniel L Hertz; Jeremy Ash; Alexandra Larson; Lisa A Carey; Howard L McLeod; Alison A Motsinger-Reif Journal: Pharmacogenet Genomics Date: 2021-02-01 Impact factor: 2.000
Authors: Dennis A Simpson; Nathalay Lemonie; David S Morgan; Shobhan Gaddameedhi; William K Kaufmann Journal: Cancers (Basel) Date: 2015-06-17 Impact factor: 6.639