Prediction of the efficacy of adjuvant radiotherapy for early endometrioid uterine cancer based on polymorphism of genes affecting oxidative stress

Uterine cancer (UC) ranks first among malignant neoplasms of the female reproductive system. Despite the high proportion of early detection, the effectiveness of adjuvant radiotherapy remains variable, which necessitates the search for molecular prognostic markers. In this study, we assessed the prognostic significance of single nucleotide polymorphisms (SNPs) of genes regulating oxidative stress in the context of disease-free survival (DFS) in patients with stage I endometrioid UC who received combined treatment. The study included 93 patients who underwent surgery and adjuvant radiotherapy. Genotyping of common polymorphic variants of the APOE (rs429358, rs7412), COMT (rs4680), HFE (rs1800562) and PON-1 (rs662) genes was performed using PCR with subsequent restriction. A statistically significant association was established between the rs662 genotype of the PON-1 gene and DFS (p=0.01), as well as pronounced trends for the COMT rs4680 and HFE rs1800562 polymorphisms. The multiple regression model including these SNPs demonstrated a high correlation with DFS (R=0.99; p<0.00001). However, discriminant analysis did not reveal sufficient prognostic value of the model for clinical use. The obtained results indicate a potential role of polymorphisms of genes controlling oxidative stress in predicting the response to radiotherapy in patients with stage I endometrioid radiotherapy after surgical treatment, but require confirmation in larger studies. © 2025 Elsevier B.V., All rights reserved.