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

PLoS One. 2013 May 21;8(5):e64716. doi: 10.1371/journal.pone.0064716. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Disease-Free Survival
  • European Continental Ancestry Group / genetics
  • Female
  • Gene Frequency / genetics
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / genetics*
  • Hodgkin Disease / pathology
  • Humans
  • Karyopherins / genetics
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Nuclear Receptor Coactivators / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Karyopherins
  • MicroRNAs
  • NCOA6 protein, human
  • Nuclear Receptor Coactivators
  • XPO5 protein, human

Grant support

This work was supported by a grant from Fondo de Investigaciones Sanitarias/Instituto de Salud Carlos III (FIS-PI0900547). Rut Tejero is an APIF fellow of the University of Barcelona. Marina Díaz-Beyá is supported by Sociedad Española de Hematología y Hemoterapia (SEHH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.