A sequence polymorphism in miRNA-608 predicts recurrence after radiotherapy of nasopharyngeal carcinoma
Menée sur 837 patients atteints d'un carcinome rhinopharyngé traité par radiothérapie, puis validée sur 828 autres patients, cette étude chinoise montre qu'un polymorphisme à simple nucléotide du micro-ARN 608 peut prédire le risque de récidive
Nasopharyngeal carcinoma (NPC) 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 (SNPs) in mature microRNA (miRNA) sequences have the potential to exert broad impact since miRNAs target many mRNAs. The aim of this study was to evaluate the effects of SNPs in mature miRNA sequences on clinical outcome in NPC patients receiving radiotherapy. In particular, we analyzed associations between seven SNPs and NPC locoregional recurrence (LRR) in 837 patients from eastern China, validating the findings in an additional 828 patients from southern China. We found that miRNA-608 rs4919510C>G exhibited a consistent association with LRR in the discovery set (hazard ratio [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 data set (HR=2.08; 95%CI=1.41-3.26). Biochemical investigations demonstrated that rs4919510C>G affects expression of miRNA-608 target genes along with NPC 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 miRNA-608 as a simple marker to predict locoregional recurrence in radiotherapy-treated NPC patients.
Cancer Research , résumé, 2013