[Cellular and neoplastic otorhinolaryngologic changes, molecular markers and therapeutic potential].
Head and neck cancer is believed to arise after accumulation of genetic alterations resulting at least partially from chronic exposure of the upper aerodigestive tract to tobacco carcinogens. Accumulation of somatic genetic events in genes implicated in cell growth and differentiation lead to cell transformation and to the acquisition of cancer phenotype. The most frequent alterations in head and neck cancer results from chromosomal instability with amplification and deletion of recurrent chromosome arms. Among the genes that drives head and neck carcinogenesis, TP53 mutations, p16 deletion or hypermethylation, amplification of cyclinD1 and overexpression of the epidermal growth factor receptor are of the most importance and will be discuss in this review. Correlation between genetic alterations and clinical parameters will be underlined. Indeed, the identification of molecular alterations linked to specific tumor parameters may be of help in the management of head and neck cancer patients or useful in the development of new therapeutic strategies. Finally, studies have shown that in some part, constitutional genetic background could also interfere with the development of head and neck cancer through the existence of polymorphisms in carcinogens metabolizing enzymes and/or DNA repair enzymes. Individuals with low carcinogens elimination or DNA repair capacities could therefore be at risk of head and neck cancer. In this review both aspects of head and neck carcinogenesis will be discuss and relation between fundamental research and clinical practice will be mentioned.
Blons
H
H
U490 INSERM Laboratoire de Toxicologie Moléculaire, 45 rue des Saints Pères, 75006 Paris.
Laccourreye
O
O
Laurent-Puig
P
P
D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D015870:Gene Expression / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D014029:Tobacco Use Disorder / Q000150:complications