title: DNA methylation changes associated with risk factors in tumors of the upper aerodigestive tract.
abstract: 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.
authors.affiliation: International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Samson
authors.initials: S
authors.lastname: Mani
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szymańska
authors.forename: Cyrille
authors.initials: C
authors.lastname: Cuenin
authors.forename: David
authors.initials: D
authors.lastname: Zaridze
authors.forename: Karen
authors.initials: K
authors.lastname: Balassiano
authors.forename: Sheila C S
authors.initials: SC
authors.lastname: Lima
authors.forename: Elena
authors.initials: E
authors.lastname: Matos
authors.forename: Alexander
authors.initials: A
authors.lastname: Daudt
authors.forename: Sergio
authors.initials: S
authors.lastname: Koifman
authors.forename: Victor Wunsch
authors.initials: VW
authors.lastname: Filho
authors.forename: Ana M B
authors.initials: AM
authors.lastname: Menezes
authors.forename: Maria Paula
authors.initials: MP
authors.lastname: Curado
authors.forename: Gilles
authors.initials: G
authors.lastname: Ferro
authors.forename: Thomas
authors.initials: T
authors.lastname: Vaissière
authors.forename: Bakary S
authors.initials: BS
authors.lastname: Sylla
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.forename: Luis Felipe Ribeiro
authors.initials: LF
authors.lastname: Pinto
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Herceg
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000428:Alcohol Drinking; D016022:Case-Control Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking