Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment.

2.50
Hdl Handle:
http://hdl.handle.net/10541/58677
Title:
Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment.
Authors:
Badie, Christophe; Dziwura, S; Raffy, C; Tsigani, Theodora; Alsbeih, G; Moody, J; Finnon, Paul; Levine, Edward; Scott, David A; Bouffler, Simon
Abstract:
Normal tissue reactions to radiation therapy vary in severity among patients and cannot be accurately predicted, limiting treatment doses. The existence of heritable radiosensitivity syndromes suggests that normal tissue reaction severity is determined, at least in part, by genetic factors and these may be revealed by differences in gene expression. To test this hypothesis, peripheral blood lymphocyte cultures from 22 breast cancer patients with either minimal (11) or very severe acute skin reactions (11) have been used to analyse gene expression. Basal and post-irradiation expression of four radiation-responsive genes (CDKN1A, GADD45A, CCNB1, and BBC3) was determined by quantitative real-time PCR in T-cell cultures established from the two patient groups before radiotherapy. Relative expression levels of BBC3, CCNB1, and GADD45A 2 h following 2 Gy X-rays did not discriminate between groups. However, post-irradiation expression response was significantly reduced for CDKN1A (P<0.002) in severe reactors compared to normal. Prediction of reaction severity of approximately 91% of individuals sampled was achieved using this end point. Analysis of TP53 Arg72Pro and CDKN1A Ser31Arg single nucleotide polymorphisms did not show any significant association with reaction sensitivity. Although these results require confirmation and extension, this study demonstrates the possibility of predicting the severity of acute skin radiation toxicity in simple tests.
Affiliation:
Radiation Effects Department, Health Protection Agency, Centre for Radiation Chemical and Environmental Hazards, Radiation Protection Division, Chilton, Didcot, Oxfordshire OX11 ORQ, UK. christophe.badie@hpa.org.uk
Citation:
Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment. 2008, 98 (11):1845-51 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
3-Jun-2008
URI:
http://hdl.handle.net/10541/58677
DOI:
10.1038/sj.bjc.6604381
PubMed ID:
18493234
Type:
Article
Language:
en
ISSN:
1532-1827
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research; Clinical Oncology

Full metadata record

DC FieldValue Language
dc.contributor.authorBadie, Christophe-
dc.contributor.authorDziwura, S-
dc.contributor.authorRaffy, C-
dc.contributor.authorTsigani, Theodora-
dc.contributor.authorAlsbeih, G-
dc.contributor.authorMoody, J-
dc.contributor.authorFinnon, Paul-
dc.contributor.authorLevine, Edward-
dc.contributor.authorScott, David A-
dc.contributor.authorBouffler, Simon-
dc.date.accessioned2009-04-01T22:54:57Z-
dc.date.available2009-04-01T22:54:57Z-
dc.date.issued2008-06-03-
dc.identifier.citationAberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment. 2008, 98 (11):1845-51 Br. J. Canceren
dc.identifier.issn1532-1827-
dc.identifier.pmid18493234-
dc.identifier.doi10.1038/sj.bjc.6604381-
dc.identifier.urihttp://hdl.handle.net/10541/58677-
dc.description.abstractNormal tissue reactions to radiation therapy vary in severity among patients and cannot be accurately predicted, limiting treatment doses. The existence of heritable radiosensitivity syndromes suggests that normal tissue reaction severity is determined, at least in part, by genetic factors and these may be revealed by differences in gene expression. To test this hypothesis, peripheral blood lymphocyte cultures from 22 breast cancer patients with either minimal (11) or very severe acute skin reactions (11) have been used to analyse gene expression. Basal and post-irradiation expression of four radiation-responsive genes (CDKN1A, GADD45A, CCNB1, and BBC3) was determined by quantitative real-time PCR in T-cell cultures established from the two patient groups before radiotherapy. Relative expression levels of BBC3, CCNB1, and GADD45A 2 h following 2 Gy X-rays did not discriminate between groups. However, post-irradiation expression response was significantly reduced for CDKN1A (P<0.002) in severe reactors compared to normal. Prediction of reaction severity of approximately 91% of individuals sampled was achieved using this end point. Analysis of TP53 Arg72Pro and CDKN1A Ser31Arg single nucleotide polymorphisms did not show any significant association with reaction sensitivity. Although these results require confirmation and extension, this study demonstrates the possibility of predicting the severity of acute skin radiation toxicity in simple tests.en
dc.language.isoenen
dc.subjectGene Expressionen
dc.subjectRadiation Therapyen
dc.subjectNormal Tissue Responseen
dc.subjectLymphocyteen
dc.subjectBreast Canceren
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshApoptosis Regulatory Proteins-
dc.subject.meshBreast Neoplasms-
dc.subject.meshCyclin B-
dc.subject.meshCyclin-Dependent Kinase Inhibitor p21-
dc.subject.meshFemale-
dc.subject.meshGenes, p53-
dc.subject.meshHumans-
dc.subject.meshMiddle Aged-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshProto-Oncogene Proteins-
dc.subject.meshRadiation Tolerance-
dc.subject.meshTranscription, Genetic-
dc.titleAberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment.en
dc.typeArticleen
dc.contributor.departmentRadiation Effects Department, Health Protection Agency, Centre for Radiation Chemical and Environmental Hazards, Radiation Protection Division, Chilton, Didcot, Oxfordshire OX11 ORQ, UK. christophe.badie@hpa.org.uken
dc.identifier.journalBritish Journal of Canceren

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