Endothelin receptor type B gene promoter hypermethylation in salivary rinses is independently associated with risk of oral cavity cancer and premalignancy

Kavita Malhotra Pattani, Zhe Zhang, Semra Demokan, Chad Glazer, Myriam Loyo, Steven Goodman, David Sidransky, Francisco Bermudez, Germain Jean-Charles, Thomas McCaffrey, Tapan Padhya, Joan Phelan, Silvia Spivakovsky, Helen Yoo Bowne, Judith D. Goldberg, Linda Rolnitzky, Miriam Robbins, A. Ross Kerr, David Sirois, Joseph A. Califano

Research output: Contribution to journalArticle

Abstract

Endothelin receptor type B (EDNRB) and kinesin family member 1A (KIF1A) are candidate tumor suppressor genes that are inactivated in cancers. In this study, we evaluated the promoter hypermethylation of EDNRB and KIF1A 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 EDNRB and KIF1A 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 KIF1A or EDNRB methylation. Methylation of EDNRB highly correlated with that of KIF1A (P < 0.0001). On multivariable modeling, histologic diagnosis was independently associated with EDNRB (P = 0.0003) or KIF1A (P = 0.027) methylation. A subset of patients analyzed (n = 161) without prior biopsy-proven malignancy received clinical risk classification based on examination. On univariate analysis, EDNRB and risk classification were associated with diagnosis of dysplasia/cancer and remained significant on multivariate analysis (EDNRB: P = 0.047, risk classification: P = 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 EDNRB methylation improved to 75%. EDNRB 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.

Original languageEnglish (US)
Pages (from-to)1093-1103
Number of pages11
JournalCancer Prevention Research
Volume3
Issue number9
DOIs
StatePublished - Sep 2010

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Endothelin B Receptors
Mouth Neoplasms
Mouth
Kinesin
Methylation
Genes
Neoplasms
Tooth
Tumor Suppressor Genes
Multivariate Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Endothelin receptor type B gene promoter hypermethylation in salivary rinses is independently associated with risk of oral cavity cancer and premalignancy. / Pattani, Kavita Malhotra; Zhang, Zhe; Demokan, Semra; Glazer, Chad; Loyo, Myriam; Goodman, Steven; Sidransky, David; Bermudez, Francisco; Jean-Charles, Germain; McCaffrey, Thomas; Padhya, Tapan; Phelan, Joan; Spivakovsky, Silvia; Bowne, Helen Yoo; Goldberg, Judith D.; Rolnitzky, Linda; Robbins, Miriam; Kerr, A. Ross; Sirois, David; Califano, Joseph A.

In: Cancer Prevention Research, Vol. 3, No. 9, 09.2010, p. 1093-1103.

Research output: Contribution to journalArticle

Pattani, KM, Zhang, Z, Demokan, S, Glazer, C, Loyo, M, Goodman, S, Sidransky, D, Bermudez, F, Jean-Charles, G, McCaffrey, T, Padhya, T, Phelan, J, Spivakovsky, S, Bowne, HY, Goldberg, JD, Rolnitzky, L, Robbins, M, Kerr, AR, Sirois, D & Califano, JA 2010, 'Endothelin receptor type B gene promoter hypermethylation in salivary rinses is independently associated with risk of oral cavity cancer and premalignancy', Cancer Prevention Research, vol. 3, no. 9, pp. 1093-1103. https://doi.org/10.1158/1940-6207.CAPR-10-0115
Pattani, Kavita Malhotra ; Zhang, Zhe ; Demokan, Semra ; Glazer, Chad ; Loyo, Myriam ; Goodman, Steven ; Sidransky, David ; Bermudez, Francisco ; Jean-Charles, Germain ; McCaffrey, Thomas ; Padhya, Tapan ; Phelan, Joan ; Spivakovsky, Silvia ; Bowne, Helen Yoo ; Goldberg, Judith D. ; Rolnitzky, Linda ; Robbins, Miriam ; Kerr, A. Ross ; Sirois, David ; Califano, Joseph A. / Endothelin receptor type B gene promoter hypermethylation in salivary rinses is independently associated with risk of oral cavity cancer and premalignancy. In: Cancer Prevention Research. 2010 ; Vol. 3, No. 9. pp. 1093-1103.
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abstract = "Endothelin receptor type B (EDNRB) and kinesin family member 1A (KIF1A) are candidate tumor suppressor genes that are inactivated in cancers. In this study, we evaluated the promoter hypermethylation of EDNRB and KIF1A 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 EDNRB and KIF1A 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 KIF1A or EDNRB methylation. Methylation of EDNRB highly correlated with that of KIF1A (P < 0.0001). On multivariable modeling, histologic diagnosis was independently associated with EDNRB (P = 0.0003) or KIF1A (P = 0.027) methylation. A subset of patients analyzed (n = 161) without prior biopsy-proven malignancy received clinical risk classification based on examination. On univariate analysis, EDNRB and risk classification were associated with diagnosis of dysplasia/cancer and remained significant on multivariate analysis (EDNRB: P = 0.047, risk classification: P = 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 EDNRB methylation improved to 75{\%}. EDNRB 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.",
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AU - Demokan, Semra

AU - Glazer, Chad

AU - Loyo, Myriam

AU - Goodman, Steven

AU - Sidransky, David

AU - Bermudez, Francisco

AU - Jean-Charles, Germain

AU - McCaffrey, Thomas

AU - Padhya, Tapan

AU - Phelan, Joan

AU - Spivakovsky, Silvia

AU - Bowne, Helen Yoo

AU - Goldberg, Judith D.

AU - Rolnitzky, Linda

AU - Robbins, Miriam

AU - Kerr, A. Ross

AU - Sirois, David

AU - Califano, Joseph A.

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