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Title: MiR-SNPs as markers of toxicity and clinical outcome in Hodgkin Lymphoma patients
Author: Navarro Ponz, Alfons
Muñoz, Carmen
Gaya, Anna
Díaz Beyà, Marina
Gel, Bernat
Tejero Villalba, Rut
Díaz Sánchez, Tania
Martínez Pozo, Antonio
Monzó Planella, Mariano
Keywords: Malaltia de Hodgkin
Micro RNAs
Hodgkin's disease
Issue Date: 21-May-2013
Publisher: Public Library of Science (PLoS)
Abstract: 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.
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It is part of: PLoS One, 2013, vol. 8, num. 5, p. e64716
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Fonaments Clínics)

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