Ethmoid Sinus Adenocarcinoma Clinical Trial
Official title:
Mechanisms of Cancerogenesis for Woodworkers Adenocarcinomas: Transcriptional Study of Olfactory Cleft Cells of Patients Exposed or Not to Wood Dust
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.
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.
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