Single nucleotide polymorphisms, apoptosis, and the development of severe late adverse effects after radiotherapy.

Details

Serval ID
serval:BIB_E894A2187610
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Single nucleotide polymorphisms, apoptosis, and the development of severe late adverse effects after radiotherapy.
Journal
Clinical Cancer Research
Author(s)
Azria D., Ozsahin M., Kramar A., Peters S., Atencio D.P., Crompton N.E., Mornex F., Pèlegrin A., Dubois J.B., Mirimanoff R.O., Rosenstein B.S.
ISSN
1078-0432
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
14
Number
19
Pages
6284-6288
Language
english
Abstract
PURPOSE: Evidence has accumulated in recent years suggestive of a genetic basis for a susceptibility to the development of radiation injury after cancer radiotherapy. The purpose of this study was to assess whether patients with severe radiation-induced sequelae (RIS; i.e., National Cancer Institute/CTCv3.0 grade, > or =3) display both a low capacity of radiation-induced CD8 lymphocyte apoptosis (RILA) in vitro and possess certain single nucleotide polymorphisms (SNP) located in candidate genes associated with the response of cells to radiation. EXPERIMENTAL DESIGN: DNA was isolated from blood samples obtained from patients (n = 399) included in the Swiss prospective study evaluating the predictive effect of in vitro RILA and RIS. SNPs in the ATM, SOD2, XRCC1, XRCC3, TGFB1, and RAD21 genes were screened in patients who experienced severe RIS (group A, n = 16) and control subjects who did not manifest any evidence of RIS (group B, n = 18). RESULTS: Overall, 13 and 21 patients were found to possess a total of <4 and > or =4 SNPs in the candidate genes. The median (range) RILA in group A was 9.4% (5.3-16.5) and 94% (95% confidence interval, 70-100) of the patients (15 of 16) had > or =4 SNPs. In group B, median (range) RILA was 25.7% (20.2-43.2) and 33% (95% confidence interval, 13-59) of patients (6 of 18) had > or =4 SNPs (P < 0.001). CONCLUSIONS: The results of this study suggest that patients with severe RIS possess 4 or more SNPs in candidate genes and low radiation-induced CD8 lymphocyte apoptosis in vitro.
Keywords
Apoptosis, CD8-Positive T-Lymphocytes/metabolism, Case-Control Studies, Fibrosis, Genetic Predisposition to Disease, Genotype, Humans, Neoplasms/genetics, Neoplasms/pathology, Polymorphism, Single Nucleotide, Radiation Injuries/diagnosis, Radiation Injuries/genetics, Radiation Tolerance/genetics, Radiotherapy/adverse effects, Risk, Time Factors, Treatment Outcome
Pubmed
Web of science
Open Access
Yes
Create date
15/10/2009 8:04
Last modification date
20/08/2019 16:11
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