Data from <i>Endothelin Receptor Type B</i> Gene Promoter Hypermethylation in Salivary Rinses Is Independently Associated with Risk of Oral Cavity Cancer and Premalignancy

Abstract

<div>Abstract<p><i>Endothelin receptor type B</i> (<i>EDNRB</i>) and <i>kinesin family member 1A</i> (<i>KIF1A</i>) are candidate tumor suppressor genes that are inactivated in cancers. In this study, we evaluated the promoter hypermethylation of <i>EDNRB</i> and <i>KIF1A</i> and their potential use for risk classification in prospectively collected salivary rinses from patients with premalignant/malignant oral cavity lesions. Quantitative methylation-specific PCR was performed to analyze the methylation status of <i>EDNRB</i> and <i>KIF1A</i> in salivary rinses of 191 patients. We proceeded to determine the association of methylation status with histologic diagnosis and estimate classification accuracy. On univariate analysis, diagnosis of dysplasia/cancer was associated with age and <i>KIF1A</i> or <i>EDNRB</i> methylation. Methylation of <i>EDNRB</i> highly correlated with that of <i>KIF1A</i> (<i>P</i> < 0.0001). On multivariable modeling, histologic diagnosis was independently associated with <i>EDNRB</i> (<i>P</i> = 0.0003) or <i>KIF1A</i> (<i>P</i> = 0.027) methylation. A subset of patients analyzed (<i>n</i> = 161) without prior biopsy-proven malignancy received clinical risk classification based on examination. On univariate analysis, <i>EDNRB</i> and risk classification were associated with diagnosis of dysplasia/cancer and remained significant on multivariate analysis (<i>EDNRB</i>: <i>P</i> = 0.047, risk classification: <i>P</i> = 0.008). Clinical risk classification identified dysplasia/cancer with a sensitivity of 71% and a specificity of 58%. The sensitivity of clinical risk classification combined with <i>EDNRB</i> methylation improved to 75%. <i>EDNRB</i> methylation in salivary rinses was independently associated with histologic diagnosis of premalignancy and malignancy and may have potential in classifying patients at risk for oral premalignant and malignant lesions in settings without access to a skilled dental practitioner. This may also potentially identify patients with premalignant and malignant lesions that do not meet the criteria for high clinical risk based on skilled dental examination. Cancer Prev Res; 3(9); 1093–103. ©2010 AACR.</p></div>