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Molecular epidemiology study on sino-nasal cancer: p53 mutations

The role of occupational exposure to wood dust in causation of sino-nasal cancer has long been established by numerous epidemiological studies, with the highest risks, in some earlier studies extremely high ones, observed for hardrwood dusts and adenocarcinoma histology. Mechanisms by which exposure to wood dust increases the risk of sino-nasal cancer (SNC) are nevertheless largely unknown.

The present study involved a large collection of SNC tumours, to our knowledge by far the largest one studied so far (>400 cases), collected in three Eurpean countries (Denmark, Finland and France) which vary in major types of woodworking industries and principle types of wood species used.

The tumours included in the study underwent a common review of histo-pathological diagnoses carried out by a panel of pathologists.

The on-going study revealed a very high frequency of TP53 mutations (70-80 %) in sino-nasal tumours. Our preliminary data shows that mutation frequency was highest in adenocarcinoma, the cell type known to exhibit highly elevated risk ratios for occupationally hardwood dust exposure. Also, the mutation frequencies and types exhibit some variation according to country.

Additional immunohistochemistry analyses were performed. After completion of exposure assessment (occupational exposure histories and tobacco smoke exposure) will allow analysis of relationships between occupational wood dust exposure and mutations. In summary, based on our current molecular analysis, it appears apparent that mutational mechanisms are frequently involved in the process of tumourigenesis in SNC.

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FINNISH INSTITUTE OF OCCUPATIONAL HEALTH
Topeliuksenkatu 41 a
00250 Helsinki
Finland
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