A sequence polymorphism in miR-608 predicts recurrence after radiotherapy for nasopharyngeal carcinoma.

Abstract

Nasopharyngeal carcinoma is treated with radiotherapy and other modalities, but there is little information on individual genetic factors to help predict and improve patient outcomes. Single-nucleotide polymorphisms (SNP) in mature microRNA (miRNA) sequences have the potential to exert broad impact as miRNAs target many mRNAs. The aim of this study was to evaluate the effects of SNPs in mature miRNA sequences on clinical outcome in patients with nasopharyngeal carcinoma receiving radiotherapy. In particular, we analyzed associations between seven SNPs and nasopharyngeal carcinoma locoregional recurrence (LRR) in 837 patients from eastern China, validating the findings in an additional 828 patients from southern China. We found that miR-608 rs4919510C > G exhibited a consistent association with LRR in the discovery set [HR, 2.05; 95% confidence interval (CI), 1.35-3.21], the validation set (HR, 2.24; 95% CI, 1.45-3.38), and the combined dataset (HR, 2.08; 95% CI, 1.41-3.26). Biochemical investigations showed that rs4919510C > G affects expression of miR-608 target genes along with nasopharyngeal carcinoma cell growth after irradiation in vivo and in vitro. Notably, X-ray radiation induced more chromatid breaks in lymphocyte cells from rs4919510CC carriers than in those from subjects with other genotypes (P = 0.0024). Our findings reveal rs4919510C > G in miR-608 as a simple marker to predict LRR in patients with radiotherapy-treated nasopharyngeal carcinoma.