BACKGROUND: 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, ras mutations were suggested to be related to wood dust exposure, but these studies were too limited to detect statistically significant associations. METHODS: 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-ras 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. RESULTS: 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-ras 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. CONCLUSION: Patients exposed to wood dust seemed more likely to develop adenocarcinoma compared to squamous cell carcinomas. K-ras mutations were detected in 13% of adenocarcinomas. In this study and previously published studies of sinonasal cancer the found K-ras mutations, were almost exclusively G --> A transitions. In conclusion, our study, based on a large representative collection of human SNC tumours, indicates that K-ras 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-ras mutations in development of sinonasal cancer.
A new comprehensive data linkage system for the detailed investigation of occupational cancer has been established in the Danish Cancer Registry, providing employment histories back to 1964. All 382 cases of cancers of the sinonasal cavities diagnosed between 1970 and 1984 and kept on file in this data linkage system were analysed using standardised proportional incidence ratios (SPIR) to screen for industrial high risk areas for these malignancies in Denmark. Excess risks were confirmed among men and women employed in the manufacture of footwear and other leather products and of wooden furniture. No risk significantly above expectancy was observed among wood workers outside the furniture making industry. Excess risks were also seen among men in all areas of basic metal industries (SPIR = 184-562) and in a subset of workers in industries producing metal containers (SPIR = 329-600). Most unexpected were raised risks among employees of both sexes in making cocoa, chocolate, and sugar confectionery (SPIR = 535 for men and 860 for women); these, in combination with the observed risks among female employees in canning and preserving fruits and vegetables (SPIR = 778) and in farming (SPIR = 735) may point to a common aetiology. The obscuring effect of mass significance may, however, be another explanation. The new associations discovered in this large scale linkage study must therefore await further confirmation.
In order to study the connection between occupation and sinonasal cancer we have reviewed the files and histological sections of 70 patients (24 females and 46 males) treated at the Department of Oto-rhino-laryngology, National Hospital of Norway. Detailed information concerning previous occupations was obtained by telephone interviews according to a standardized questionnaire. This pilot study revealed a strong association between wood dust exposure and sinonasal cancer. Of 12 wood dust exposed men, 11 had been exposed exclusively to softwood. While squamous cell carcinoma was the predominant type of cancer in joiners, carpenters and loggers, non-Hodgkin lymphomas appeared to be associated with employment in saw- and planingmill firms. A nationwide case-control study is under preparation for further substantiation of the health hazards connected with exposure to softwood and other possible occupational factors related to sinonasal cancer.
A case-control study of 121 men seen for cancer of the nasal cavity or paranasal sinuses in British Columbia between 1939 and 1977 showed increased relative risks associated with occupations involving exposure to wood (2.5) and with smoking (4.9). The occupations involved were chiefly forestry and carpentry. Both risk factors appeared to be associated with the principal sites within the nasal cavity paranasal sinuses and with most histologic subtypes of cancer.
Notes
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