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MiR-SNPs as Markers of Toxicity and Clinical Outcome in Hodgkin Lymphoma Patients

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  • Alfons Navarro
  • Carmen Muñoz
  • Anna Gaya
  • Marina Díaz-Beyá
  • Bernat Gel
  • Rut Tejero
  • Tania Díaz
  • Antonio Martinez
  • Mariano Monzó

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.

Suggested Citation

  • Alfons Navarro & Carmen Muñoz & Anna Gaya & Marina Díaz-Beyá & Bernat Gel & Rut Tejero & Tania Díaz & Antonio Martinez & Mariano Monzó, 2013. "MiR-SNPs as Markers of Toxicity and Clinical Outcome in Hodgkin Lymphoma Patients," PLOS ONE, Public Library of Science, vol. 8(5), pages 1-10, May.
    • Handle: RePEc:plo:pone00:0064716
    DOI: 10.1371/journal.pone.0064716
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    References listed on IDEAS

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    1. Thimmaiah P. Chendrimada & Richard I. Gregory & Easwari Kumaraswamy & Jessica Norman & Neil Cooch & Kazuko Nishikura & Ramin Shiekhattar, 2005. "TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing," Nature, Nature, vol. 436(7051), pages 740-744, August.
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    Cited by:

    1. Lingzi Xia & Yangwu Ren & Xue Fang & Zhihua Yin & Xuelian Li & Wei Wu & Peng Guan & Baosen Zhou, 2014. "Prognostic Role of Common MicroRNA Polymorphisms in Cancers: Evidence from a Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(10), pages 1-8, October.
    2. Mu-Peng Li & Yao-Dong Hu & Xiao-Lei Hu & Yan-Jiao Zhang & Yong-Long Yang & Chun Jiang & Jie Tang & Xiao-Ping Chen, 2016. "MiRNAs and miRNA Polymorphisms Modify Drug Response," IJERPH, MDPI, vol. 13(11), pages 1-22, November.

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