TP53 and EGFR mutations in combination with lifestyle risk factors in tumours of the upper aerodigestive tract from South America

Autor(es):Mostrar menos -

Szymanska, K. ; Levi, J. E. ^[1] ; Menezes, A. ^[2] ; Wuensch-Filho, V. ^[1] ; Eluf-Neto, J. ^[1] ; Koifman, S. ^[3] ; Matos, E. ^[4] ; Daudt, A. W. ^[5] ; Curado, M. P. ^[6] ; Villar, S. ; Pawlita, M. ^[7] ; Waterboer, T. ^[7] ; Boffetta, P. ; Hainaut, P. ; Brennan, P. ^[8]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, BR-01246904 Sao Paulo - Brazil

^[2] Univ Fed Pelotas, BR-96020220 Pelotas - Brazil

^[3] Fundacao Oswaldo Cruz, Escola Nacl Saude Publ, BR-21041210 Rio De Janeiro - Brazil

^[4] Univ Buenos Aires, Dept Carcinogenesis Quim, RA-1417 Buenos Aires, DF - Argentina

^[5] Hosp Clin Porto Alegre, BR-90035903 Porto Alegre, RS - Brazil

^[6] Goiania Canc Registry, Goiania, Go - Brazil

^[7] German Canc Res Ctr, Infect & Canc F020, D-69120 Heidelberg - Germany

^[8] Int Agcy Res Canc, Genet Sect, F-69008 Lyon - France

• Tipo de documento: Artigo Científico
• Fonte: Carcinogenesis; v. 31, n. 6, p. 1054-1059, JUN 2010.
• Citações Web of Science: 14

Resumo

Cancers of the upper aerodigestive tract {[}(UADT): oral cavity, pharynx, larynx and oesophagus] have high incidence rates in some parts of South America. Alterations in the TP53 gene are common in these cancers. In our study, we have estimated the prevalence and patterns of TP53 mutations (exons 4-10) in 236 UADT tumours from South America in relation to lifestyle risk factors, such as tobacco smoking and alcohol drinking. Moreover, we have conducted a pilot study of EGFR mutations (exons 18-21) in 45 tumours from the same population. TP53 mutation prevalence was high: 59% of tumours were found to carry mutant TP53. We found an association between TP53 mutations and tobacco smoking and alcohol drinking. The mutation rate increased from 38% in never-smokers to 66% in current smokers (P-value for trend = 0.09). G:C > T:A transversions were found only in smokers (15%). Alcohol drinkers carried more G:C > A:T transitions (P = 0.08). Non-exposed individuals were more probable to carry G:C > A:T transitions at CpG sites (P = 0.01 for never-smokers and P < 0.001 for never-drinkers). EGFR mutations were found in 4% of cases. Inactivation of TP53 by mutations is a crucial molecular event in the UADT carcinogenesis and it is closely related to exposure to lifestyle risk factors. EGFR mutations do not appear to be a common event in UADT carcinogenesis in this population. (AU)

• Processo FAPESP: 01/01768-2 - Estudo internacional de fatores ambientais, vírus e câncer de cavidade oral e de laringe
• Beneficiário: José Eluf Neto
• Modalidade de apoio: Auxílio à Pesquisa - Regular