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Mechanisms of Cancerogenesis of Woodworkers Adenocarcinomas (ADK-FO)

5 februari 2018 bijgewerkt door: Central Hospital, Nancy, France

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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Observationeel

Inschrijving (Werkelijk)

28

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Frankrijk
      • Vandoeuvre Les Nancy, Frankrijk, 54511
        • Service ORL-CHRU NANCY

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

50 jaar tot 120 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Ja

Geslachten die in aanmerking komen voor studie

Mannelijk

Bemonsteringsmethode

Niet-waarschijnlijkheidssteekproef

Studie Bevolking

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

Beschrijving

Inclusion Criteria:

  • Male, > 50 years
  • No known tumor
  • patient needing fiberendoscopy, but for nasal pathology
  • informed consent given
  • affiliation to a healthcare scheme compulsory
  • prior medical exam 'NON EXPOSED' group: no wood dust exposure 'EXPOSED' group : wood dust exposure > 20 years with delay since the beginning of exposure > 30 years

Exclusion criteria:

  • Prior radiotherapy on sinus or nasal fossa
  • Inflammatory disease of nasal fossa
  • Genetic disease with cancer risk (xeroderma pigmentosum, chromosomal abnormality deletion or translocation, DNA repair deficiency)
  • No informed consent
  • No affiliation to a healthcare scheme compulsory
  • prior medical exam
  • Contra-indication to Xylocaine

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

Cohorten en interventies

Groep / Cohort
Interventie / Behandeling
NON EXPOSED

Male, >50 years, unexposed to wood dust, without any nasal pathology, without known tumor

-> Brushing of the olfactory cleft
Ander: Brushing of the olfactory cleft
Non invasive sampling of olfactory cleft cells, by brushing under local anesthesia during fiberendoscopy Form: survey of acceptability
EXPOSED

Male, >50 years, exposed to wood dust, without any nasal pathology, without known tumor

-> Brushing of the olfactory cleft
Ander: Brushing of the olfactory cleft
Non invasive sampling of olfactory cleft cells, by brushing under local anesthesia during fiberendoscopy Form: survey of acceptability

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
The identification of expression profiles specific of wood dust exposure (comparison of both groups (exposed / non exposed))
Tijdsspanne: through study completion, an average of 1 year
Descriptive data (Mean, Median, Min, Max). Comparison of gene expression levels ( Ttest ) of both groups: identification of expression profiles specific of each group (Ftest)
through study completion, an average of 1 year

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
The identification of expression profiles predictive of a nasal adenocarcinoma transformation.
Tijdsspanne: through study completion, an average of 1 year
Comparison of gene expression levels of the 15 exposed patients with known gene expression levels of 15 tumor samples (intestinal adenocarcinomas related to wood dust) (T Test) Identification of common modifications of gene expression (Ftest)
through study completion, an average of 1 year
The acceptability of the brushing technique
Tijdsspanne: through study completion, an average of 1 year

The acceptability will be evaluated on a composite criterion with three sub-criteria

  • subjective representation of the utility of the screening (mean >5/10)
  • subjective evaluation of the acceptability (pain, discomfort, complication) (mean>5/10)
  • agreement for an eventual second sample (>90%) All sub-criteria must be fulfilled to meet this outcome
through study completion, an average of 1 year

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Central Hospital, Nancy, France

Onderzoekers

  • Hoofdonderzoeker: Patrice Gallet, MD, CHRU NANCY

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 juni 2016

Primaire voltooiing (Werkelijk)

1 september 2016

Studie voltooiing (Werkelijk)

1 maart 2017

Studieregistratiedata

Eerst ingediend

23 mei 2016

Eerst ingediend dat voldeed aan de QC-criteria

27 juni 2016

Eerst geplaatst (Schatting)

29 juni 2016

Updates van studierecords

Laatste update geplaatst (Werkelijk)

6 februari 2018

Laatste update ingediend die voldeed aan QC-criteria

5 februari 2018

Laatst geverifieerd

1 juni 2016

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 2015-A02004-45

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

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