Polymorphism in mature microRNA-608 sequence is associated with an increased risk of nasopharyngeal carcinoma

Accumulative evidences indicated that microRNAs (miRNAs) can function as tumor suppressors and oncogenes, in which genetic variations are implicated in various cancer susceptibilities. However, it remains unclear whether single nucleotide polymorphisms (SNPs) in mature miRNA sequence alter nasopharyngeal carcinoma (NPC) susceptibility. In this study, we analyzed associations between eight SNPs in miRNA mature sequences (i.e., rs37464441>C in hsa-mir-499, rs4919510C>G in hsa-mir-608, rs13299349G>A in hsa-mir-3152, rs12220909G>C in hsa-mir-4293, rs2168518G>A in hsa-mir-4513, rs8078913T>C in hsa-mir-4520a, rs11237828T>C in hsa-mir-5579, and rs9295535T>C in hsa-mir-5689) and NPC susceptibility in southern China with 906 NPC cases and 1072 cancer-free controls, and validated the significant findings in eastern China with 684 cases and 907 healthy controls. Functional assays were further performed to identity the biological effects of these polymorphisms. We found that rs4919510C>G polymorphism showed a consistent association with NPC risk in southern China (GC + GG versus CC genotype, odds ratio [OR] = 1.36, 95% confidence interval [Cl] = 1.10-1.70) and eastern China (GC + GG versus CC: OR = 137,95% Cl = 1.08-1.74). After the two populations were merged, the ORs and 95% CI were 1.38 and 1.18 to 1.62, respectively. Moreover, the rs4919510C>G adverse genotypes significantly interacted with Epstein-Barr virus (EBV) infection on increasing NPC risk (P = 0.001). The functional assay further showed that the CNE-2 cell lines that transfected with miR-608-rs4919510G allele expression vector exerted more colony number formations than cell lines that transfected with miR-608-rs4919510C allele expression vector (P = 0.001). These data suggested that rs4919510C>G of miR-608 may be a susceptible biomarker of NPC in China. (C) 2015 Elsevier B.V. All rights reserved.