K-<it>ras </it>mutations in sinonasal cancers in relation to wood dust exposure

<p>Abstract</p> <p>Background</p> <p>Cancer in the sinonasal tract is rare, but persons who have been occupationally exposed to wood dust have a substantially increased risk. It has been estimated that approximately 3.6 million workers are exposed to inhalable wood dust...

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Main Authors: Luce Danièle, Holmila Reetta, Schlünssen Vivi, Wolff Henrik, Antonsen Annemarie, Dictor Michael, Steiniche Torben, Hansen Johnni, Bornholdt Jette, Vogel Ulla, Husgafvel-Pursiainen Kirsti, Wallin Håkan
Format: Article
Language:English
Published: BMC 2008-02-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/8/53
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author Luce Danièle
Holmila Reetta
Schlünssen Vivi
Wolff Henrik
Antonsen Annemarie
Dictor Michael
Steiniche Torben
Hansen Johnni
Bornholdt Jette
Vogel Ulla
Husgafvel-Pursiainen Kirsti
Wallin Håkan
author_facet Luce Danièle
Holmila Reetta
Schlünssen Vivi
Wolff Henrik
Antonsen Annemarie
Dictor Michael
Steiniche Torben
Hansen Johnni
Bornholdt Jette
Vogel Ulla
Husgafvel-Pursiainen Kirsti
Wallin Håkan
author_sort Luce Danièle
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Cancer in the sinonasal tract is rare, but persons who have been occupationally exposed to wood dust have a substantially increased risk. It has been estimated that approximately 3.6 million workers are exposed to inhalable wood dust in EU. In previous small studies of this cancer, <it>ras </it>mutations were suggested to be related to wood dust exposure, but these studies were too limited to detect statistically significant associations.</p> <p>Methods</p> <p>We examined 174 cases of sinonasal cancer diagnosed in Denmark in the period from 1991 to 2001. To ensure uniformity, all histological diagnoses were carefully reviewed pathologically before inclusion. Paraffin embedded tumour samples from 58 adenocarcinomas, 109 squamous cell carcinomas and 7 other carcinomas were analysed for K-<it>ras </it>codon 12, 13 and 61 point mutations by restriction fragment length polymorphisms and direct sequencing. Information on occupational exposure to wood dust and to potential confounders was obtained from telephone interviews and from registry data.</p> <p>Results</p> <p>Among the patients in this study, exposure to wood dust was associated with a 21-fold increased risk of having an adenocarcinoma than a squamous cell carcinoma compared to unexposed [OR = 21.0, CI = 8.0–55.0]. K-<it>ras </it>was mutated in 13% of the adenocarcinomas (seven patients) and in 1% of squamous cell carcinomas (one patient). Of these eight mutations, five mutations were located in the codon 12. The exact sequence change of remaining three could not be identified unambiguously. Among the five identified mutations, the G→A transition was the most common, and it was present in tumour tissue from two wood dust exposed adenocarcinoma patients and one patient with unknown exposure. Previously published studies of sinonasal cancer also identify the GGT → GAT transition as the most common and often related to wood dust exposure.</p> <p>Conclusion</p> <p>Patients exposed to wood dust seemed more likely to develop adenocarcinoma compared to squamous cell carcinomas. K-<it>ras </it>mutations were detected in 13% of adenocarcinomas. In this study and previously published studies of sinonasal cancer the found K-<it>ras </it>mutations, were almost exclusively G → A transitions. In conclusion, our study, based on a large representative collection of human SNC tumours, indicates that K-<it>ras </it>mutations are relatively infrequent, and most commonly occur in adenocarcinomas. Wood dust exposure alone was not found to be explanatory for the G→A mutations, but combination of exposure to tobacco, wood dust, and possibly other occupational agents may be a more likely explanation. Overall, the study suggests a limited role for K-<it>ras </it>mutations in development of sinonasal cancer.</p>
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spelling doaj.art-9d057ae91efb435b9060a09eb39a590d2022-12-22T03:27:29ZengBMCBMC Cancer1471-24072008-02-01815310.1186/1471-2407-8-53K-<it>ras </it>mutations in sinonasal cancers in relation to wood dust exposureLuce DanièleHolmila ReettaSchlünssen ViviWolff HenrikAntonsen AnnemarieDictor MichaelSteiniche TorbenHansen JohnniBornholdt JetteVogel UllaHusgafvel-Pursiainen KirstiWallin Håkan<p>Abstract</p> <p>Background</p> <p>Cancer in the sinonasal tract is rare, but persons who have been occupationally exposed to wood dust have a substantially increased risk. It has been estimated that approximately 3.6 million workers are exposed to inhalable wood dust in EU. In previous small studies of this cancer, <it>ras </it>mutations were suggested to be related to wood dust exposure, but these studies were too limited to detect statistically significant associations.</p> <p>Methods</p> <p>We examined 174 cases of sinonasal cancer diagnosed in Denmark in the period from 1991 to 2001. To ensure uniformity, all histological diagnoses were carefully reviewed pathologically before inclusion. Paraffin embedded tumour samples from 58 adenocarcinomas, 109 squamous cell carcinomas and 7 other carcinomas were analysed for K-<it>ras </it>codon 12, 13 and 61 point mutations by restriction fragment length polymorphisms and direct sequencing. Information on occupational exposure to wood dust and to potential confounders was obtained from telephone interviews and from registry data.</p> <p>Results</p> <p>Among the patients in this study, exposure to wood dust was associated with a 21-fold increased risk of having an adenocarcinoma than a squamous cell carcinoma compared to unexposed [OR = 21.0, CI = 8.0–55.0]. K-<it>ras </it>was mutated in 13% of the adenocarcinomas (seven patients) and in 1% of squamous cell carcinomas (one patient). Of these eight mutations, five mutations were located in the codon 12. The exact sequence change of remaining three could not be identified unambiguously. Among the five identified mutations, the G→A transition was the most common, and it was present in tumour tissue from two wood dust exposed adenocarcinoma patients and one patient with unknown exposure. Previously published studies of sinonasal cancer also identify the GGT → GAT transition as the most common and often related to wood dust exposure.</p> <p>Conclusion</p> <p>Patients exposed to wood dust seemed more likely to develop adenocarcinoma compared to squamous cell carcinomas. K-<it>ras </it>mutations were detected in 13% of adenocarcinomas. In this study and previously published studies of sinonasal cancer the found K-<it>ras </it>mutations, were almost exclusively G → A transitions. In conclusion, our study, based on a large representative collection of human SNC tumours, indicates that K-<it>ras </it>mutations are relatively infrequent, and most commonly occur in adenocarcinomas. Wood dust exposure alone was not found to be explanatory for the G→A mutations, but combination of exposure to tobacco, wood dust, and possibly other occupational agents may be a more likely explanation. Overall, the study suggests a limited role for K-<it>ras </it>mutations in development of sinonasal cancer.</p>http://www.biomedcentral.com/1471-2407/8/53
spellingShingle Luce Danièle
Holmila Reetta
Schlünssen Vivi
Wolff Henrik
Antonsen Annemarie
Dictor Michael
Steiniche Torben
Hansen Johnni
Bornholdt Jette
Vogel Ulla
Husgafvel-Pursiainen Kirsti
Wallin Håkan
K-<it>ras </it>mutations in sinonasal cancers in relation to wood dust exposure
BMC Cancer
title K-<it>ras </it>mutations in sinonasal cancers in relation to wood dust exposure
title_full K-<it>ras </it>mutations in sinonasal cancers in relation to wood dust exposure
title_fullStr K-<it>ras </it>mutations in sinonasal cancers in relation to wood dust exposure
title_full_unstemmed K-<it>ras </it>mutations in sinonasal cancers in relation to wood dust exposure
title_short K-<it>ras </it>mutations in sinonasal cancers in relation to wood dust exposure
title_sort k it ras it mutations in sinonasal cancers in relation to wood dust exposure
url http://www.biomedcentral.com/1471-2407/8/53
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