MiR-SNPs as markers of toxicity and clinical outcome in Hodgkin lymphoma patients

• Published in: PloS one Vol. 8; no. 5; p. e64716
• Main Authors: Navarro, Alfons, Muñoz, Carmen, Gaya, Anna, Díaz-Beyá, Marina, Gel, Bernat, Tejero, Rut, Díaz, Tania, Martinez, Antonio, Monzó, Mariano
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.05.2013; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biology; Biomarkers, Tumor - metabolism; Biosynthesis; Bleomycin; Cancer therapies; Care and treatment; Chemotherapy; Chromosomes; Clinical outcomes; Disease-Free Survival; Embryology; Epidemiology; European Continental Ancestry Group - genetics; Female; Gene Frequency - genetics; Genes; Genetic aspects; Genomes; Genomics; Genotypes; Hematology; Hodgkin Disease - drug therapy; Hodgkin Disease - genetics; Hodgkin Disease - pathology; Hodgkin's disease; Hodgkin's lymphoma; Humans; Karyopherins - genetics; Laboratories; Limfomes; Lymphoma; Lymphomas; Malaltia de Hodgkin; Male; Markers; Medical prognosis; Medical treatment; Medicine; Micro RNAs; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Multiple myeloma; Multivariate Analysis; Mutation; Neoplasm Staging; Neutropenia; Non-Hodgkin's lymphomas; Nuclear Receptor Coactivators - genetics; Oncology; Patient outcomes; Patients; Polymorphism, Single Nucleotide - genetics; Precision medicine; Radiation therapy; Ribonucleic acid; RNA; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Survival; Toxic diseases; Toxicity; Treatment Outcome; Tumors; Young Adult; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0064716

In recent years, microRNA (miRNA) pathways have emerged as a crucial system for the regulation of tumorogenesis. miR-SNPs are a novel class of single nucleotide polymorphisms that can affect miRNA pathways. We analyzed eight miR-SNPs by allelic discrimination in 141 patients with Hodgkin lymphoma and correlated the results with treatment-related toxicity, response, disease-free survival (DFS) and overall survival (OS). The KRT81 (rs3660) GG genotype was associated with an increased risk of neurological toxicity (P = 0.016), while patients with XPO5 (rs11077) AA or CC genotypes had a higher rate of bleomycin-associated pulmonary toxicity (P = 0.048). Both miR-SNPs emerged as independent factors in the multivariate analysis. The XPO5 AA and CC genotypes were also associated with a lower response rate (P = 0.036). XPO5 (P = 0.039) and TRBP (rs784567) (P = 0.022) genotypes emerged as prognostic markers for DFS, and XPO5 was also associated with OS (P = 0.033). In the multivariate analysis, only XPO5 emerged as an independent prognostic factor for DFS (HR: 2.622; 95%CI 1.039-6.620; P = 0.041). Given the influence of XPO5 and TRBP as individual markers, we then investigated the combined effect of these miR-SNPs. Patients with both the XPO5 AA/CC and TRBP TT/TC genotypes had the shortest DFS (P = 0.008) and OS (P = 0.008). miR-SNPs can add useful prognostic information on treatment-related toxicity and clinical outcome in Hodgkin lymphoma and can be used to identify patients likely to be chemoresistant or to relapse.