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.

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.

SUBMITTER: Navarro A 

PROVIDER: S-EPMC3660374 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature