Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer.
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.
Holmila
Reetta
R
Finnish Institute of Occupational Health, Helsinki, Finland.
Bornholdt
Jette
J
Heikkilä
Pirjo
P
Suitiala
Tuula
T
Févotte
Joëlle
J
Cyr
Diane
D
Hansen
Johnni
J
Snellman
Satu-Marja
SM
Dictor
Michael
M
Steiniche
Torben
T
Schlünssen
Vivi
V
Schneider
Thomas
T
Pukkala
Eero
E
Savolainen
Kai
K
Wolff
Henrik
H
Wallin
Håkan
H
Luce
Danièle
D
Husgafvel-Pursiainen
Kirsti
K
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
D004391:Dust