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MiR-SNPs as markers of toxicity and clinical outcome in Hodgkin Lymphoma patients
Navarro Ponz, Alfons; Muñoz, C.; Gaya, A.; Díaz-Beyá, Marina; Gel, B.; Tejero Villalba, Rut; Díaz, T.; Martínez Pozo, Antonio; Monzó Planella, Mariano
Universitat de Barcelona
Background: 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. Design and Methods: 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). Results: 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). Conclusion: 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.
Malaltia de Hodgkin
Micro RNAs
Limfomes
Hodgkin's disease
MicroRNAs
Lymphomas
cc-by (c) Navarro Ponz, Alfons et al., 2013
http://creativecommons.org/licenses/by/3.0/es
Artículo
info:eu-repo/semantics/publishedVersion
Public Library of Science (PLoS)
         

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