Authors: Juliette Sheridan Miriam Tosetto Julie Gorman Diarmuid O’Donoghue Kieran Sheahan John Hyland Hugh Mulcahy David Gibbons Jacintha O’Sullivan
Publish Date: 2012/10/14
Volume: 44, Issue: 1, Pages: 41-45
Abstract
Defects in DNA repair pathways have been linked with colorectal cancer CRC Adjuvant radiotherapy has become commonplace in the treatment of rectal cancer however it is associated with a higher rate of second cancer formation It is known that radiation results in DNA damage directly or indirectly by radiationinduced bystander effect RIBE by causing doublestrand breaks DSBs The majority of work in RIBE has been performed in cell lines and limited studies have been in or ex vivoThe first study aim was to examine by immunohistochemistry levels of DSB expression of the protein MRE11 in normal colonic tissue outside the irradiated field post neoadjuvant radiotherapy group 1 These levels were compared to a irradiated tumour tissue post neoadjuvant radiation within the same group b a CRC patient group group 2 who had not undergone neoadjuvant radiotherapy and c a noncancer patient group group 3 The second aim was to determine if MRE11 expression levels were related to survival or radiosensitivity post neoadjuvant radiotherapyOur findings show radiotherapy causes DSBs at significantly higher levels in normal colonic mucosa of patients post neoadjuvant treatment which may represent RIBE If this damage remains unrepaired increased levels of genomic instability may contribute to the higher occurrence of second cancers in patients treated post neoadjuvant radiotherapy
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