Lymphocyte radiosensitivity inBRCA1 andBRCA2 mutation carriers and implications for breast cancer susceptibility
| العنوان: | Lymphocyte radiosensitivity inBRCA1 andBRCA2 mutation carriers and implications for breast cancer susceptibility |
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| المؤلفون: | Caroline Langman, Zsofia Kote-Jarai, A Georgiou, Rosalind A. Eeles, I Kesterton, Imogen Locke, Ashi Salmon, Richard Camplejohn, Elizabeth Bancroft, Shirley Hodgson, Audrey Arden-Jones, J Berg, Zoe Docherty, Laurent Pangon, Ellen Solomon, J Barwell, Joanna R. Morris |
| المصدر: | International Journal of Cancer. 121:1631-1636 |
| بيانات النشر: | Wiley, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Adult, G2 Phase, Heterozygote, Cancer Research, medicine.medical_specialty, Time Factors, endocrine system diseases, DNA repair, Lymphocyte, Apoptosis, Breast Neoplasms, Biology, medicine.disease_cause, S Phase, Breast cancer, medicine, Humans, Genetic Predisposition to Disease, Lymphocytes, Radiosensitivity, skin and connective tissue diseases, BRCA2 Protein, Mutation, BRCA1 Protein, Cell Cycle, Cytogenetics, Cancer, Chromosome Breakage, medicine.disease, Kinetics, medicine.anatomical_structure, Oncology, Cancer research, Female, Chromosome breakage |
| الوصف: | There is conflicting evidence as to whether individuals who are heterozygous for germ-line BRCA1 or BRCA2 mutations have an altered phenotypic cellular response to irradiation. To investigate this, chromosome breakage and apoptotic response were measured after irradiation in peripheral blood lymphocytes from 26 BRCA1 and 18 BRCA2 mutation carriers without diagnosed breast cancer, and 38 unaffected age, ethnically and sex-matched controls. To assess the role of BRCA1 and BRCA2 in homologous recombination, an S phase enrichment chromosome breakage assay was used. BrdUrd incorporation studies allowed verification of the correct experimental settings. We found that BRCA1 mutation carriers without cancer had increased chromosome breaks as well as breaks and gaps per cell post irradiation using the classical G2 assay (p = 0.01 and 0.004, respectively) and the S phase enrichment assay (p = 0.01 and 0.01, respectively) compared to age-matched unaffected controls. BRCA2 mutation carriers without cancer had increased breaks as well as breaks and gaps per cell post irradiation using the S phase enrichment assay (p = 0.045 and 0.012, respectively). No difference was detected using the G2 assay (p = 0.88 and 0.40 respectively). BRCA1 and BRCA2 mutation carriers had normal cell cycle kinetics and apoptotic response to irradiation compared to age-matched controls. Our results show a demonstrable impairment in irradiation induced DNA repair in women with heterozygous germline BRCA1 and BRCA2 mutations prior to being diagnosed with breast cancer. |
| تدمد: | 1097-0215 0020-7136 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1e2847c93b6a30c4ece901a2785c1c3eTest https://doi.org/10.1002/ijc.22915Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1e2847c93b6a30c4ece901a2785c1c3e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970215 00207136 |
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