Oligogenic Determinism of Colorectal Cancer

Cancer Clinical Trial

— DOCC  

Official title:

Oligogenic Determinism of Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01057953
• Other study ID #: 2009/082/HP
• Status: Completed
• Phase: N/A
• First received: January 27, 2010
• Last updated: October 15, 2013
• Start date: January 2010
• Est. completion date: January 2013

Study information

• Verified date: October 2013
• Source: University Hospital, Rouen
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

The majority of the clinical situations suggestive of an increased genetic risk for colorectal cancer (CRC) are not explained by a simple monogenic model. Our working hypothesis is that a fraction of clinical conditions suggestive of an increased genetic risk for CRC (familial aggregation, early age of tumour onset, development of multiple primary CRC) is due to the combination of a limited number of genetic variations, each conferring a moderate risk for CRC, but whose combination results into high risk.

This study, which will be both retrospective and prospective, is an association study that will compare frequencies of selected genetic variations, alone or in combination, between patients (cases) whose clinical presentation is suggestive of an increased genetic risk but who do not present a known Mendelian form of CRC, and controls, in order to assess associations of these variations with non-Mendelian genetic forms of CRC. The inclusion criteria will be: CRC in two first degree relatives, one being diagnosed before 61 years of age; or CRC diagnosed before 51 years of age or advanced colorectal adenoma before 41 years of age; or multiple primary CRCs in the same individual, the first being diagnosed before 61 years of age The exclusion criteria will be: Lynch syndrome, adenomatous polyposis and hamartomatous polyposis. The genetic variations which will be analyzed will include (i) SNPs detected by GWAS and associated to CRC. (ii) Risk factors corresponding to functional polymorphisms within candidate genes. (iii) Imbalance of the TGFbR1 allelic expression. Sample sizes were calculated to obtain 80% power for an odds ratio of 2.5 since the aim of this study is to determine genetic variations conferring a moderate risk. In order to cover all these possibilities and to have reasonable even for the genetic variations with low frequency below 0.03 or high frequency above 0.90, the target sample size was set at 700 cases and 350 controls. The recruitment of patients will be performed at the national level by the cancer genetics departments ensuring a correct evaluation of the personal and familial history and the French molecular diagnosis laboratories network ensuring in routine the analysis of the main genes involved in CRC. The control population will be composed of healthy subjects of Caucasian origin between 45 and 60 years of age, without personal or familial history among their first-degree relatives of colorectal tumours.

Demonstration that the combination of a limited number of genetic variations, each conferring a moderate risk for CRC, results into high risk would allow to base, in selected families, the evaluation of risk in relatives and indication of colonoscopy on the analysis of gene variants the combination of which would confer a high risk. This study will confirm or invalidate the contribution of aTGFbR1 allelic expression imbalance in the determinism of early-onset CRC and familial aggregation of CRC. The demonstration of the involvement in CRC genetic variations with strong effect of specific combinations should be of interest for our general understanding of the molecular basis of CRC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1550
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 61 Years

Eligibility

Inclusion Criteria:

• colorectal cancer (CRC) in two first degree relatives, one being diagnosed before 61 years of age

• CRC diagnosed before 51 years of age or advanced colorectal adenoma before 41 years of age

• multiple primary CRCs in the same individual, the first being diagnosed before 61 years of age.

Exclusion Criteria:

• Lynch syndrome,

• adenomatous polyposis defined by more than 10 adenomas histologically proved,

• hamartomatous polyposis defined by one hamartoma histologically proved,

• absence of informed consent.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Cancer
• Colorectal Neoplasms

Intervention

Genetic:
• Blood drawn
Blood drawn for patient

Locations

Country	Name	City	State
France	Centre François Baclesse	Caen
France	CHU de Dijon	Dijon
France	CHU de Grenoble	Grenoble
France	CHRU de Lille	Lille
France	CHU de Montpellier	Montpellier
France	CLCC Val d'Aurelle	Montpellier
France	CH de Niort	Niort
France	Hôpital Européen Georges Pompidou	Paris
France	Institut Curie	Paris
France	Centre Eugène Marquis	Rennes
France	CHU de Rennes	Rennes
France	UHRouen	Rouen
France	CHU de Saint-Etienne	Saint-Etienne
France	CHU de Toulouse	Toulouse
France	Institut Claudius Regaud	Toulouse
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Rouen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	genetic variation assessment		once	No