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Carcinogenesis Advance Access published online on November 9, 2009
Carcinogenesis, doi:10.1093/carcin/bgp277
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

MicroRNA Expression in Head and Neck Cancer Associates with Alcohol Consumption and Survival

Michele Avissar1, Michael D. McClean3, Karl T. Kelsey1,2 and Carmen J. Marsit1

1 Department of Pathology and Laboratory Medicine
2 Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI
3 Department of Environmental Health, Boston University School of Public Health, Boston MA

Request for reprints: Carmen J. Marsit, PhD, Assistant Professor, Department of Pathology and Laboratory Medicine, Brown University Division of Biology and Medicine, Box G-E5, Providence, RI 02912; Phone: 401-863-6508; Fax: 401-863-9008; E-mail: carmen_marsit{at}brown.edu.

The contribution of microRNAs (miRNAs) to carcinogenesis in many tumors, including head and neck squamous cell carcinomas (HNSCCs) is clear, but the etiology and clinical significance of their alteration remain important questions. Our previous work has identified four microRNAs (miRNAs) as differentially expressed HNSCCs compared to non-diseased epithelia and showed that there is potential diagnostic utility in examining their expression. Here, we used quantitative real-time PCR to determine the relative expression of these miRNAs in a larger, independent case-series of HNSCC tumors (n = 169), examining associations of miRNA expression with exposures and clinical features associated with HNSCC. In multivariate analyses, expression of miR-375 was shown to increase with alcohol consumption (P = 0.002), and showed higher expression in tumors of pharyngeal and laryngeal origin compared with oral tumors (P < 0.05 and P < 0.01, respectively). Additionally, high miR-21 expression was associated with significantly decreased 5-year survival in patients (HR, 1.68; 95% CI 1.04-2.77) in a model controlled for patient age, gender, and tumor stage. Together, these data suggest that alterations in miRNA expression are related to exposures causal in head and neck cancer and may be useful biomarkers of patient outcome.

Key Words: microRNA • Head and Neck Cancer • alcohol

Received July 27, 2009; revised October 29, 2009; accepted October 30, 2009.


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