Increased Chromosomal Radiosensitivity in Women Carrying BRCA1/BRCA2 Mutations Assessed With the G2 Assay

Journal Article · Mon Mar 15 00:00:00 EDT 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2009.10.020· OSTI ID:21372181

Ernestos, Beroukas ^[1]; Nikolaos, Pandis ^[2]; Koulis, Giannoukakos ^[3]; Eleni, Rizou ^[1]; Konstantinos, Beroukas ^[4]; Alexandra, Giatromanolaki ^[5]; Michael, Koukourakis ^[6]

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1. Radiotherapy Department, Metropolitan Hospital, Athens (Greece)
2. Department of Genetics, 'Agios Savvas' Cancer Hospital, Athens (Greece)
3. Biology Department, National Centre of Scientific Research 'Demokritos', Athens (Greece)
4. Radiotherapy Department, 'Agios Savvas' Cancer Hospital, Athens (Greece)
5. Department of Pathology, Demokritus University of Thrace, Alexandroupolis (Greece)
6. Radiotherapy Department, Demokritus University of Thrace, Alexandroupolis (Greece)

Purpose: Several in vitro studies suggest that BRCA1 and BRCA2 mutation carriers present increased sensitivity to ionizing radiation. Different assays for the assessment of deoxyribonucleic acid double-strand break repair capacity have been used, but results are rather inconsistent. Given the concerns about the possible risks of breast screening with mammography in mutation carrier women and the potentially damaging effects of radiotherapy, the purpose of this study was to further investigate the radiosensitivity of this population. Methods and Materials: The G2 chromosomal radiosensitivity assay was used to assess chromosomal breaks in lymphocyte cultures after exposure to 1 Gy. A group of familiar breast cancer patients carrying a mutation in the BRCA1 or BRCA2 gene (n = 15) and a group of healthy mutation carriers (n = 5) were investigated and compared with a reference group of healthy women carrying no mutation (n = 21). Results: BRCA1 and BRCA2 mutation carriers had a significantly higher number of mean chromatid breaks per cell (p = 0.006) and a higher maximum number of breaks (p = 0.0001) as compared with their matched controls. Both healthy carriers and carriers with a cancer history were more radiosensitive than controls (p = 0.002 and p = 0.025, respectively). Age was not associated with increased radiosensitivity (p = 0.868). Conclusions: Our results indicate that BRCA1 and BRCA2 mutation carriers show enhanced radiosensitivity, presumably because of the involvement of the BRCA genes in deoxyribonucleic acid repair and cell cycle control mechanisms.

• OSTI ID: 21372181
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 76, Issue 4; Other Information: DOI: 10.1016/j.ijrobp.2009.10.020; PII: S0360-3016(09)03411-7; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
62 RADIOLOGY AND NUCLEAR MEDICINE
BIOMEDICAL RADIOGRAPHY
CARRIERS
CELL CYCLE
CONTROL
DNA REPAIR
GENES
LYMPHOCYTES
MAMMARY GLANDS
MUTATIONS
RADIOSENSITIVITY
RADIOTHERAPY
STRAND BREAKS
WOMEN
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CONNECTIVE TISSUE CELLS
DIAGNOSTIC TECHNIQUES
DNA DAMAGES
FEMALES
GLANDS
LEUKOCYTES
MAMMALS
MAN
MATERIALS
MEDICINE
NUCLEAR MEDICINE
ORGANS
PRIMATES
RADIOLOGY
REPAIR
SENSITIVITY
SOMATIC CELLS
THERAPY
VERTEBRATES