TY - JOUR
T1 - Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer
AU - Holmila, Reetta
AU - Bornholdt, Jette
AU - Heikkilä, Pirjo
AU - Suitiala, Tuula
AU - Févotte, Joëlle
AU - Cyr, Diane
AU - Hansen, Johnni
AU - Snellman, Satu-Marja
AU - Dictor, Michael
AU - Steiniche, Torben
AU - Schlünssen, Vivi
AU - Schneider, Thomas
AU - Pukkala, Eero
AU - Savolainen, Kai
AU - Wolff, Henrik
AU - Wallin, Håkan
AU - Luce, Danièle
AU - Husgafvel-Pursiainen, Kirsti
N1 - Keywords: Adenocarcinoma; Aged; Carcinoma, Squamous Cell; Dust; Electrophoresis, Capillary; Female; Genes, p53; Humans; Male; Middle Aged; Mutation; Nose Neoplasms; Occupational Exposure; Paranasal Sinuses; Wood
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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 (≥24 years, OR 5.1, 95% CI, 1.5-17.1), average level (>2 mg/m3; OR 3.6, 95% CI, 1.2-10.8) and cumulative level (≥30 mg/m3 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.
AB - 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 (≥24 years, OR 5.1, 95% CI, 1.5-17.1), average level (>2 mg/m3; OR 3.6, 95% CI, 1.2-10.8) and cumulative level (≥30 mg/m3 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.
U2 - 10.1002/ijc.25064
DO - 10.1002/ijc.25064
M3 - Journal article
C2 - 19950227
SN - 0020-7136
VL - 127
SP - 578
EP - 588
JO - Radiation Oncology Investigations
JF - Radiation Oncology Investigations
IS - 3
ER -
