Efeitos actínicos tardios no câncer de próstata e o gene XRCC3

Abstract

Introduction: Prostate cancer is the most common malignant neoplasm in men in Brazil, and radiotherapy (RT) represents one of the main therapeutic modalities for localized disease. Ionizing radiation promotes DNA damage, especially double-strand breaks (DSBs), considered one of the most serious forms of genetic damage. Considering its role in homologous recombination, the XRCC3 gene presents itself as a candidate gene to be related to the individual radiosensitivity profile. Methods: A literature review on the subject was conducted using the PUBMED database on the XRCC3 gene and its association with the side effects of radiotherapy in cancer patients, with greater emphasis on prostate cancer. Only 14 published articles were found, with publication dates from 2008 onwards, of which 9 were included in this analysis. Results: Studies evaluating the XRCC3 gene and its association with the late effects of radiotherapy have included patients with various tumor types. Burri et al. (2008) evaluated prostate cancer patients in a retrospective cohort of 135 individuals and demonstrated that the combination of the SOD2 rs4880 C/T and XRCC3 rs861539 T/C (Thr241Met) genotypes led to a significant increase in grade 2 late rectal bleeding compared to patients without this specific genotypic arrangement (14% vs. 1%; p=0.002). In that study, 76.3% of patients underwent implantation and 23.7% underwent implantation combined with external beam radiotherapy, with a median follow-up of 53 months (range: 12–140 months). In the systematic review and meta-analysis by Song et al. (2015), 17 articles were evaluated; the rs1799794 variant was shown to be a protective factor against late effects (OR = 0.47, 95% CI: 0.26–0.86, p = 0.01), while rs861539 showed a statistical association with the occurrence of acute radiation-induced effects (OR = 1.99, 95% CI: 1.31–3.01, p = 0.001) but no overall association with late effects; the review included articles evaluating pelvic tumors. Conclusion: Despite its role in homologous recombination, there are still few studies in the literature that include single nucleotide polymorphisms of the XRCC3 gene and their relationship with the occurrence of late effects of radiotherapy in patients with prostate cancer, especially the SNP rs861539. However, the existing findings reinforce the need to continue the analysis of this topic, since the genetic profile of radiosensitive individuals has not yet been determined and the data already collected indicate the participation of the XRCC3 gene in this process.