Abstract
The purpose of this study was to evaluate the association between ATM, TP53 and MDM2 polymorphisms in prostate cancer patients and morbidity after radiotherapy. The presence of ATM (rs1801516), TP53 (rs1042522, rs1800371, rs17878362, rs17883323, and rs35117667), and MDM2 (rs2279744) polymorphisms was assessed by direct sequencing of PCR fragments from 48 patients with histologically proven prostate adenocarcinoma and treated with external beam radiation. The side effects were classified according to the Radiation Therapy Oncology Group (RTOG) score. The results showed no association between clinical characteristics and the development of radiation toxicities (P > 0.05). The C>T transition in the position 16273 (intron 3) of TP53 (rs35117667) was significantly associated with the risk of acute skin toxicity (OR: 0.0072, 95% CI 0.0002–0.227, P = 0.003). The intronic TP53 polymorphism at position 16250 (rs17883323) was associated with chronic urinary toxicity (OR: 0.071, 95%CI 0.006–0.784, P = 0.032). No significant associations were found for the remaining polymorphisms (P > 0.05). The results show that clinical characteristics were not determinant on the developing of radiation sensitivity in prostate cancer patients, and intronic TP53 polymorphisms would be associated with increased acute and chronic radiation toxicities. These observations corroborate the importance of investigating the genetic profile to predict adverse side effects in patients undergoing radiotherapy.
Highlights
Radiotherapy is the most important nonsurgical modality for the curative treatment of cancer
In response to lack of success in candidate gene studies and the subsequent recognition that this approach is too limited in scope, radiogenomic investigators have begun a much broader search to identify genes and single nucleotide polymorphisms (SNP) associated with radiation response
Several large-scale genome wide association (GWA) studies have been initiated in which radiotherapy patients are being genotyped for large numbers of common SNPs [8, 43]
Summary
Radiotherapy is the most important nonsurgical modality for the curative treatment of cancer. The success of radiotherapy in eradicating a tumor depends mainly on the total radiation dose given, but the tolerance of the normal tissues surrounding the tumor limits this dose. There is a significant variation between patients regarding the severity of toxicity following a given dose of radiotherapy. The dose is submaximal in the majority of the radiotherapy patients [1]. Chronic side effects from radiotherapy are often irreversible and can decrease health-related quality of life as well as limit treatment intensity in radical radiotherapy regimens. Quantification of acute and chronic toxicity is crucial in the assessment of the therapeutic benefit of radiotherapy. Various studies worldwide have attempted to identify common genetic variations associated with the development of radiation toxicity as a step in the process of identifying such a subset of toxicity prone patients [2, 3]
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