title: MiR-SNPs as markers of toxicity and clinical outcome in Hodgkin lymphoma patients.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain. anavarroponz@ub.edu
authors.forename: Alfons
authors.initials: A
authors.lastname: Navarro
authors.forename: Carmen
authors.initials: C
authors.lastname: Muñoz
authors.forename: Anna
authors.initials: A
authors.lastname: Gaya
authors.forename: Marina
authors.initials: M
authors.lastname: Díaz-Beyá
authors.forename: Bernat
authors.initials: B
authors.lastname: Gel
authors.forename: Rut
authors.initials: R
authors.lastname: Tejero
authors.forename: Tania
authors.initials: T
authors.lastname: Díaz
authors.forename: Antonio
authors.initials: A
authors.lastname: Martinez
authors.forename: Mariano
authors.initials: M
authors.lastname: Monzó
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D028884:Karyopherins / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D056918:Nuclear Receptor Coactivators / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016896:Treatment Outcome; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D028884:Karyopherins; D035683:MicroRNAs; C486559:NCOA6 protein, human; D056918:Nuclear Receptor Coactivators; C446511:XPO5 protein, human