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Articles by M Avissar
Total Records ( 3 ) for M Avissar
  B. C Christensen , B. J Moyer , M Avissar , L. G Ouellet , S. L Plaza , M. D McClean , C. J Marsit and K. T. Kelsey
 

MicroRNA (miRNA)-binding site polymorphisms that could contribute to disease risk and prognosis are rapidly being identified and investigated as this genetic variation may have a potentially profound impact on human health. A recently described variant allele in the KRAS 3' untranslated region that arises in the let-7 miRNA complementary site (KRAS-LCS6) and leads to increased KRAS expression in lung cancer was examined for its association with the occurrence of head and neck squamous cell carcinoma (HNSCC). We examined the prevalence of the KRAS-LCS6 variant allele in a population-based case–control study of HNSCC to determine if this KRAS-LCS6 genotype was associated with disease occurrence and patient survival. Although the KRAS-LCS6 variant genotype was not associated with the overall risk of HNSCC, cases with the KRAS-LCS6 variant genotype had significantly reduced survival [hazard ratio (HR), 1.6; 95% confidence interval (CI), 1.0–2.5] in models controlled for confounders of survival. This risk was greatest in cases of oral cavity carcinoma (HR, 2.7; 95% CI, 1.4–5.3). These data demonstrate that cases with the KRAS-LCS6 variant have significantly reduced survival time and suggest that this variant may alter the phenotype or therapeutic response of this disease.

  M Avissar , M. D McClean , K. T Kelsey and C. J. Marsit
 

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 miRNAs as differentially expressed HNSCCs compared with non-diseased epithelia and showed that there is potential diagnostic utility in examining their expression. Here, we used quantitative real-time polymerase chain reaction 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 (hazard ratio, 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.

 
 
 
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