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Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer

Holmila, Reetta; Bornholdt, Jette; Heikkila, Pirjo; Suitiala, Tuula; Fevotte, Joelle; Cyr, Diane; Hansen, Johnni; Snellman, Satu-Marja; Dictor, Michael LU and Steiniche, Torben, et al. (2010) In International Journal of Cancer 127(3). p.578-588
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 (Cl), 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% Cl,... (More)
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 (Cl), 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% Cl, 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% Cl, 0.8-3.1). Risk of TP53 mutation was significantly increased in association with duration (>= 24 years, OR 5.1, 95% Cl, 1.5-17.1), average level (>2 mg/m(3); OR 3.6, 95% Cl, 1.2-10.8) and cumulative level (>= 30 mg/m(3) x years; OR 3.5, 95% Cl, 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. (Less)
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publication status
published
subject
keywords
wood dust, TP53, sinonasal cancer
in
International Journal of Cancer
volume
127
issue
3
pages
578 - 588
publisher
John Wiley & Sons
external identifiers
  • wos:000279131300009
  • scopus:77954452210
ISSN
0020-7136
DOI
10.1002/ijc.25064
language
English
LU publication?
yes
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c641db7e-822c-4032-b14d-23036c852ddb (old id 1630159)
date added to LUP
2010-07-23 12:31:55
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2018-07-15 03:11:52
@article{c641db7e-822c-4032-b14d-23036c852ddb,
  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 (Cl), 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% Cl, 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% Cl, 0.8-3.1). Risk of TP53 mutation was significantly increased in association with duration (>= 24 years, OR 5.1, 95% Cl, 1.5-17.1), average level (>2 mg/m(3); OR 3.6, 95% Cl, 1.2-10.8) and cumulative level (>= 30 mg/m(3) x years; OR 3.5, 95% Cl, 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.},
  author       = {Holmila, Reetta and Bornholdt, Jette and Heikkila, Pirjo and Suitiala, Tuula and Fevotte, Joelle and Cyr, Diane and Hansen, Johnni and Snellman, Satu-Marja and Dictor, Michael and Steiniche, Torben and Schlunssen, Vivi and Schneider, Thomas and Pukkala, Eero and Savolainen, Kai and Wolff, Henrik and Wallin, Hakan and Luce, Daniele and Husgafvel-Pursiainen, Kirsti},
  issn         = {0020-7136},
  keyword      = {wood dust,TP53,sinonasal cancer},
  language     = {eng},
  number       = {3},
  pages        = {578--588},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer},
  url          = {http://dx.doi.org/10.1002/ijc.25064},
  volume       = {127},
  year         = {2010},
}