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

Reetta Holmila; Jette Bornholdt; Pirjo Heikkilä; Tuula Suitiala; Joëlle Févotte; Diane Cyr; Johnni Hansen; Satu-Marja Snellman; Michael Dictor; Torben Steiniche; Vivi Schlünssen; Thomas Schneider; Eero Pukkala; Kai Savolainen; Henrik Wolff; Håkan Wallin; Danièle Luce; Kirsti Husgafvel-Pursiainen

doi:10.1002/ijc.25064

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

Reetta Holmila, Jette Bornholdt, Pirjo Heikkilä, Tuula Suitiala, Joëlle Févotte, Diane Cyr, Johnni Hansen, Satu-Marja Snellman, Michael Dictor, Torben Steiniche, Vivi Schlünssen, Thomas Schneider, Eero Pukkala, Kai Savolainen, Henrik Wolff, Håkan Wallin, Danièle Luce, Kirsti Husgafvel-Pursiainen

Glycomics Program

38 Citations (Scopus)

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 (≥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.

Original language	English
Journal	International Journal of Cancer
Volume	127
Issue number	3
Pages (from-to)	578-88
Number of pages	10
ISSN	0020-7136
DOIs	https://doi.org/10.1002/ijc.25064
Publication status	Published - 1 Aug 2010

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Holmila, R., Bornholdt, J., Heikkilä, P., Suitiala, T., Févotte, J., Cyr, D., Hansen, J., Snellman, S-M., Dictor, M., Steiniche, T., Schlünssen, V., Schneider, T., Pukkala, E., Savolainen, K., Wolff, H., Wallin, H., Luce, D., & Husgafvel-Pursiainen, K. (2010). Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer. International Journal of Cancer, 127(3), 578-88. https://doi.org/10.1002/ijc.25064

Holmila, R, Bornholdt, J, Heikkilä, P, Suitiala, T, Févotte, J, Cyr, D, Hansen, J, Snellman, S-M, Dictor, M, Steiniche, T, Schlünssen, V, Schneider, T, Pukkala, E, Savolainen, K, Wolff, H, Wallin, H, Luce, D & Husgafvel-Pursiainen, K 2010, 'Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer', International Journal of Cancer, vol. 127, no. 3, pp. 578-88. https://doi.org/10.1002/ijc.25064

@article{8269b0f08fed11df928f000ea68e967b,

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 (≥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.",

author = "Reetta Holmila and Jette Bornholdt and Pirjo Heikkil{\"a} and Tuula Suitiala and Jo{\"e}lle F{\'e}votte and Diane Cyr and Johnni Hansen and Satu-Marja Snellman and Michael Dictor and Torben Steiniche and Vivi Schl{\"u}nssen and Thomas Schneider and Eero Pukkala and Kai Savolainen and Henrik Wolff and H{\aa}kan Wallin and Dani{\`e}le Luce and Kirsti Husgafvel-Pursiainen",

note = "Keywords: Adenocarcinoma; Aged; Carcinoma, Squamous Cell; Dust; Electrophoresis, Capillary; Female; Genes, p53; Humans; Male; Middle Aged; Mutation; Nose Neoplasms; Occupational Exposure; Paranasal Sinuses; Wood",

year = "2010",

month = aug,

day = "1",

doi = "10.1002/ijc.25064",

language = "English",

volume = "127",

pages = "578--88",

journal = "Radiation Oncology Investigations",

issn = "0020-7136",

publisher = "JohnWiley & Sons, Inc.",

number = "3",

}

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 -

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

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