Mature MicroRNA Sequence Polymorphism in MIR196A2 Is Associated with Risk and Prognosis of Head and Neck Cancer

Purpose: The central role of microRNAs as regulators of translation has been well established, whereas the relationships between genetic variation in microRNAs and disease risk is only beginning to be explored. A polymorphism in the MIR196A2 locus has shown associations with lung, breast, esophageal, and gastric tumors but has not been examined in head and neck cancers, which share similar pathology and etiology to these diseases. Experimental Design: We studied a polymorphism in the mature sequence of MIR196A2 (rs11614913, C/T) in a population-based case-control study ( n = 1,039) of head and neck squamous cell carcinoma (HNSCC) to determine if MIR196A2 genotype was associated with disease occurrence and patient survival. Results: Presence of any variant allele was associated with a significantly reduced risk for HNSCC (odds ratio, 0.8; 95% confidence interval, 0.56-0.99). Homozygous variant allele carriers with pharyngeal tumors had significantly reduced survival compared with wild-type and heterozygous cases (hazard ratio, 7.4; 95% confidence interval, 1.9–28.2). Expression analysis in a subset of tumors ( n = 83) revealed no significant difference in relative expression of either miR-196a or miR-196a* by MIR196A2 genotype. Conclusion: These data demonstrate a role for MIR196A2 genotype in susceptibility and prognosis of HNSCC. Clin Cancer Res; 16(14); 3713–20. ©2010 AACR.