title: Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer.
abstract: The causal role of work-related exposure to wood dust in the development of sinonasal cancer has long been established by numerous epidemiologic studies. To study molecular changes in these tumors, we analyzed TP53 gene mutations in 358 sinonasal cancer cases with or without occupational exposure to wood dust, using capillary electrophoresis single-strand conformation polymorphism analysis and direct sequencing. A significant association between wood-dust exposure and adenocarcinoma histology was observed [adjusted odds ratio (OR) 12.6, 95% confidence interval (CI), 5.0-31.6]. TP53 mutations occurred in all histologies, with an overall frequency of 77%. TP53 mutation positive status was most common in adenocarcinoma (OR 2.0, 95% CI, 1.1-3.7; compared with squamous cell carcinoma), and mutation positivity showed an overall, nonsignificant association with wood-dust exposure (OR 1.6, 95% CI, 0.8-3.1). Risk of TP53 mutation was significantly increased in association with duration (> or =24 years, OR 5.1, 95% CI, 1.5-17.1), average level (>2 mg/m(3); OR 3.6, 95% CI, 1.2-10.8) and cumulative level (> or =30 mg/m(3) x years; OR 3.5, 95% CI, 1.2-10.7) of wood-dust exposure; adjustment for formaldehyde affected the ORs only slightly. Smoking did not influence the occurrence of TP53 mutation; however, it was associated with multiple mutations (p = 0.03). As far as we are aware, this is the first study to demonstrate a high prevalence of TP53 mutation-positive cases in a large collection of sinonasal cancers with data on occupational exposure. Our results indicate that mutational mechanisms, in particular TP53 mutations, are associated with work-related exposure to wood dust in sinonasal cancer.
authors: Finnish Institute of Occupational Health, Helsinki, Finland.
authors: Reetta
authors: R
authors: Holmila
authors: Jette
authors: J
authors: Bornholdt
authors: Pirjo
authors: P
authors: Heikkilä
authors: Tuula
authors: T
authors: Suitiala
authors: Joëlle
authors: J
authors: Févotte
authors: Diane
authors: D
authors: Cyr
authors: Johnni
authors: J
authors: Hansen
authors: Satu-Marja
authors: SM
authors: Snellman
authors: Michael
authors: M
authors: Dictor
authors: Torben
authors: T
authors: Steiniche
authors: Vivi
authors: V
authors: Schlünssen
authors: Thomas
authors: T
authors: Schneider
authors: Eero
authors: E
authors: Pukkala
authors: Kai
authors: K
authors: Savolainen
authors: Henrik
authors: H
authors: Wolff
authors: Håkan
authors: H
authors: Wallin
authors: Danièle
authors: D
authors: Luce
authors: Kirsti
authors: K
authors: Husgafvel-Pursiainen
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004391:Dust; D019075:Electrophoresis, Capillary; D005260:Female; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009669:Nose Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D016273:Occupational Exposure; D010256:Paranasal Sinuses / Q000473:pathology*; D014934:Wood
chemical_list: D004391:Dust