DNA methylation changes associated with risk factors in tumors of the upper aerodigestive tract
| Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
|---|---|
| Data(s) |
15/08/2013
15/08/2013
2012
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| Resumo |
Cancers of the upper aerodigestive tract (UADT) are common forms of malignancy associated with tobacco and alcohol exposures, although human papillomavirus and nutritional deficiency are also important risk factors. While somatically acquired DNA methylation changes have been associated with UADT cancers, what triggers these events and precise epigenetic targets are poorly understood. In this study, we applied quantitative profiling of DNA methylation states in a panel of cancer-associated genes to a case-control study of UADT cancers. Our analyses revealed a high frequency of aberrant hypermethylation of several genes, including MYOD1, CHRNA3 and MTHFR in UADT tumors, whereas CDKN2A was moderately hypermethylated. Among differentially methylated genes, we identified a new gene (the nicotinic acetycholine receptor gene) as target of aberrant hypermethylation in UADT cancers, suggesting that epigenetic deregulation of nicotinic acetycholine receptors in non-neuronal tissues may promote the development of UADT cancers. Importantly, we found that sex and age is strongly associated with the methylation states, whereas tobacco smoking and alcohol intake may also influence the methylation levels in specific genes. This study identifies aberrant DNA methylation patterns in UADT cancers and suggests a potential mechanism by which environmental factors may deregulate key cellular genes involved in tumor suppression and contribute to UADT cancers. IARC IARC la Ligue National (Francaise) Contre le Cancer la Ligue National (Francaise) Contre le Cancer National Institutes of Health/National Cancer Institute (NIH/NCI), United States National Institutes of Health/National Cancer Institute (NIH/NCI), United States Association pour la Recherche sur le Cancer (ARC, France) l'Association pour la Recherche sur le Cancer (ARC), France la Ligue Nationale (Francaise) Contre le Cancer (Comite SaoneetLoire), France la Ligue Nationale (Francaise) Contre le Cancer (Comite Saone-et-Loire), France Swiss Bridge Award Swiss Bridge Award |
| Identificador |
EPIGENETICS, AUSTIN, v. 7, n. 3, supl. 2, Part 1-2, pp. 270-277, MAR, 2012 1559-2294 http://www.producao.usp.br/handle/BDPI/32560 10.4161/epi.7.3.19306 |
| Idioma(s) |
eng |
| Publicador |
LANDES BIOSCIENCE AUSTIN |
| Relação |
EPIGENETICS |
| Direitos |
openAccess Copyright LANDES BIOSCIENCE |
| Palavras-Chave | #DNA METHYLATION #UPPER AERODIGESTIVE TRACT #CANCER #RISK FACTORS #BIOMARKERS #SQUAMOUS-CELL CARCINOMA #PROMOTER HYPERMETHYLATION #LUNG-CANCER #NECK-CANCER #SUSCEPTIBILITY LOCUS #COLORECTAL-CANCER #DIETARY-FOLATE #CPG ISLANDS #GENES #HEAD #BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Tipo |
article original article publishedVersion |
