Mechanisms of Cancerogenesis of Woodworkers Adenocarcinomas
Condition: Ethmoid Sinus Adenocarcinoma
MeSH terms: Adenocarcinoma
Study type: Observational [Patient Registry]

Summary: 
      Nasal adenocarcinomas are closely related to wood dust exposure. The precise mechanisms of
      carcinogenesis leading to the transformation of the respiratory mucosa into a colonic-like
      mucosa remain unknown: chronic exposure to wood dust may cause chronic inflammation that may
      lead to pre-degenerative lesions, hypothesis yet unconfirmed. The tumor development requires
      the activation of a particular gene: CDX2. The working hypothesis is that chronic wood dust
      exposure is responsible for changes in genes of inflammation, which can in turn lead to
      changes in the expression of CDX2 and its cofactors, thus making possible the genesis of
      adenocarcinoma. This work is a pilot study aiming to better understand the mechanisms of
      carcinogenesis, and to study the feasibility of a larger prospective screening for
      woodworkers adenocarcinomas. Cells will be obtained from the at risk area (olfactory cleft)
      by a noninvasive method (brushing) in healthy volunteers (unexposed to wood dust) and in
      exposed volunteers to compare their genomes and study the genomic changes related to wood
      dust exposure.
    

Detailed description: 
      Pilot study, single center, prospective and retrospective, aiming to better understand the
      mechanisms of carcinogenesis of nasal adenocarcinoma among 2 groups of subjects based on
      their potential risk of nasal adenocarcinoma.

      Patients will be recruited prospectively, in the ENT department (Prof. R. JANKOWSKI-Institut
      Lorrain Heart and vessels Louis Mathieu -Hospitals Brabois-CHU Nancy), during a visit for
      another medical reason.

      They will be divided into 2 groups as follows:

        -  Group 1: NON EXPOSED : control group: patients not exposed to wood dust (low risk)

        -  Group 2: EXPOSED: patients exposed to wood dust (high risk)

      After complete information, inclusion in the study will be proposed to patients

      If inclusion is accepted, patients will undergo, during the nasal fiber endoscopy (performed
      for care), and under local anesthesia (performed for care), a brushing of the most accessible
      olfactory clef (performed for research). These samples will be compared to tumor samples
      which are already available (REFCOR)

      The samples of groups 1 and 2 will be sent directly to the laboratory of Pathological Anatomy
      Cytology (Pr-J.M. VIGNAUD Hospital Brabois- CHU Nancy). They will briefly vortexed (5 min)
      and frozen. They will be kept in the laboratory of Pathological Anatomy Cytology (Pr-J.M.
      VIGNAUD Hospital Brabois- CHU Nancy) until analysis. The samples will be transferred from the
      laboratory of Pathological Anatomy Cytology (Pr-J.M. VIGNAUD Hospital Brabois- CHU Nancy) to
      the Genomics Platform (INSERM, U954, Prof. JL GUEANT- Faculty of Medicine, University of
      Lorraine), for analysis.

      RNA will be extracted from olfactory cells , using RNeasy Mini kit (Qiagen) with DNase
      treatment. The concentration and purity of the DNA / RNA will be measured (OD at 230nm, 260nm
      and 280nm) with a Nanodrop spectrophotometer (Nyxor). The RNA integrity will be determined
      from the profiles of ribosomal RNAs (18S & 28S) measured on LabOnChip® (2100 Bioanalyzer
      System, Agilent Technologies). The RNA samples will be stored at -80 ° C until use.

      The transcriptome analysis will be conducted on chips Whole Human Genome 60K * 8 developed by
      Agilent®, and according to the manufacturer's protocol (single-color Agilent protocol).

      At the end of the research samples will be destroyed.
    

Intervention name(s): Brushing of the olfactory cleft
Intervention type(s): Other
Intervention description(s): Non invasive sampling of olfactory cleft cells, by brushing under local anesthesia during fiberendoscopy Form: survey of acceptability
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Consultation requiring fiberendoscopy, planned in the ENT department of the CHRU of Nancy,
        in a context of routine care or of monitoring of professionnal wood dust exposure
      
Biospecimen description: 
      olfactory mucosae cells