Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment

Christophe Badie*, S. Dziwura, C. Raffy, T. Tsigani, G. Alsbeih, J. Moody, Paul Finnon, E. Levine, D. Scott, Simon Bouffler

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    64 Citations (Scopus)

    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 ∼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.

    Original languageEnglish
    Pages (from-to)1845-1851
    Number of pages7
    JournalBritish Journal of Cancer
    Volume98
    Issue number11
    DOIs
    Publication statusPublished - 3 Jun 2008

    Bibliographical note

    Copyright:
    Copyright 2008 Elsevier B.V., All rights reserved.

    Keywords

    • Gene expression
    • Lymphocyte
    • Normal tissue response
    • QRT-PCR (quantitative real-time polymerase chain reaction)
    • Radiation therapy
    • SNPs (single nucleotide polymorphisms)

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