Single nucleotide polymorphisms in the RNASEL gene are associated with acute and late adverse effects of radiotherapy and fatigue in patients with prostate adenocarcinoma

Abstract

Purpose: More than half of prostate cancer patients undergo radiation treatment which may be accompanied by acute or late side effects in genitourinary, GU, and/or gastrointestinal, GI tract, and radiotherapy-induced fatigue (RIF). The biological role of RNase L highlights its potential to be tested for association with the adverse effects of radiotherapy. Objectives: This study aims to investigate the associations among RNASEL gene variants, acute, late GI/GU toxicity events, and RIF to evaluate their potential to be used as biomarkers for prediction of response to radiation treatment. Methods: The DNA from peripheral blood mononuclear cells of 81 patients with prostate adenocarcinoma under RT was genotyped for RNASEL rs12757998, rs486907, and rs627928 by real-time quantitative PCR. The acute and late GU and GI adverse effects were evaluated during and up to 54 months after RT, as well as the occurrence or increase in fatigue grade. Results: rs12757998 RNASEL TT genotype was shown to be significantly associated with severity of acute GU toxicity while CT genotype with severity of late GI toxicity. Furthermore, CC genotype of rs12757998 and the AA genotype of rs627928 were shown to be potential independent predictive biomarkers of RIF. Conclusion: RNASEL gene polymorphisms are associated with a higher risk of radiotoxicity, which may be used for biological tests for the prediction of RT-related side effects and to develop strategies to fight against fatigue, to significantly improve the quality of life of cancer survivors. © Copyright © 2025 Taylor & Francis Group LLC.