Polymorphic variant TP53 (R72P) may suggest acute radiotoxicity in breast cancer patients undergoing conventional radiation treatments.

CÓRDOBA ELISA; ABBA MARTIN; LACUNZA E; E. FERNÁNDEZ; FILKENSTEIN S; A. GÜERCI

San Francisco

Congreso; ASTRO's 56st Annual Meeting.; 2014

Purpose/Objective(s): While the success of radiotherapy in eradicating a tumor depends on the total dose of radiation the tolerance of the normal tissues surrounding is the limiting factor to treatment. Regarding this the variation between patients in the severity of toxicity following a given dose of radiotherapy is important. As a result, dose is sub-maximal in many individuals because current dose thresholds are set in order to limit toxicity in those who are the most sensitive. For this reason radiation-induced toxicity is an important parameter optimization of treatment and so understanding its biological basis is essential. In the last decade numerous studies have suggested that individual radiosensitivity is a complex phenotype dependent on the interaction of multiple genes. Thus, current interest lies in developing genetic profiles that predict a patient?s probability of suffering toxicity following radiotherapy. However, it is still far from understanding the genetic basis of this trait as a whole. RADIOGENOMICS arises from the identification and clarification of all genes involved and also in developing personal genetic profiles that can predict and manage potential complications of each patient, optimizing treatment in relation to the risks associated. According to the above the aim of this study was to evaluate the potential association between single nucleotide polymorphisms related response to radiotherapy injury, such as genes related to DNA repair or enzymes involved in anti-oxidative activities. Materials/Methods: This study included 57 samples from patients with breast cancer with an average age of 58 years. All were subjected to BCS (breast conserving surgery) and subsequently treated with a dose of 5040 cGy, 180 cGy daily fractions. The treatments were conducted with accelerator Varian Clinac 4MeV. DNA extraction was performed from peripheral blood or buccal swab. All individuals were genotyped for SNPs (single nucleotide polymorphisms) in GSTP1 (I105V), NOS3 (G298A), SOD2 (V16A) and TP53 (R72P) by RFLP-PCR. The determination of the phenotypes applied the RTOG score (Radiation Therapy Oncology Group). Univariate analysis (ORs and 95% CI) was performed to correlate SNPs with the risk of developing ≥ G2 acute toxicity. Results: 66.67% of the patients reported radiotoxic effects. While it could not be demonstrated association with polymorphisms of oxidative stress enzymes tested, a significant relationship between polymorphic variant TP53 (R72P) and a risk of developing ≥ grade 1 of acute skin reactions was found (p = 0.043). Conclusions: For these reasons and given the multifactorial and polygenic trait characteristic, will continue with further study of these and other candidate genes, and the sample was expanded to identify associations between these therapies to improve and clarify the underlying mechanisms of action.