Oligogenic Determinism of Colorectal Cancer

NCT01057953 | Completed DMC

• 1 other identifier: 2009/082/HP
• Study Type: interventional
• Target: 1,550
• Locations: 1 country
• Sites: 16

Brief 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.

Conditions

Cancer

Keywords

Colo-Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• genetic variation assessment

  once

Study Arms (1)

Patient

NO INTERVENTION

Blood sample for patient included

Genetic: Blood drawn

Interventions

Blood drawn GENETIC

Blood drawn for patient

Patient

Eligibility Criteria

• Age: 18 Years - 61 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Lynch syndrome,
• adenomatous polyposis defined by more than 10 adenomas histologically proved,
• hamartomatous polyposis defined by one hamartoma histologically proved,
• absence of informed consent.

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (16)

Centre François Baclesse

Caen, 14000, France

Location

CHU de Dijon

Dijon, France

Location

CHU de Grenoble

Grenoble, France

Location

CHRU de Lille

Lille, France

Location

CHU de Montpellier

Montpellier, France

Location

CLCC Val d'Aurelle

Montpellier, France

Location

CH de Niort

Niort, France

Location

Institut Curie

Paris, 75005, France

Location

Hôpital Européen Georges Pompidou

Paris, France

Location

Centre Eugène Marquis

Rennes, 35000, France

Location

CHU de Rennes

Rennes, France

Location

UHRouen

Rouen, 76031, France

Location

CHU de Saint-Etienne

Saint-Etienne, France

Location

CHU de Toulouse

Toulouse, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Related Publications (1)

• Baert-Desurmont S, Charbonnier F, Houivet E, Ippolito L, Mauillon J, Bougeard M, Abadie C, Malka D, Duffour J, Desseigne F, Colas C, Pujol P, Lejeune S, Dugast C, Buecher B, Faivre L, Leroux D, Gesta P, Coupier I, Guimbaud R, Berthet P, Manouvrier S, Cauchin E, Prieur F, Laurent-Puig P, Lebrun M, Jonveaux P, Chiesa J, Caron O, Morin-Meschin ME, Polycarpe-Osaer F, Giraud S, Zaanan A, Bonnet D, Mansuy L, Bonadona V, El Chehadeh S, Duhoux F, Gauthier-Villars M, Saurin JC, Collonge-Rame MA, Brugieres L, Wang Q, Bressac-de Paillerets B, Rey JM, Toulas C, Buisine MP, Bronner M, Sokolowska J, Hardouin A, Cailleux AF, Sebaoui H, Blot J, Tinat J, Benichou J, Frebourg T. Clinical relevance of 8q23, 15q13 and 18q21 SNP genotyping to evaluate colorectal cancer risk. Eur J Hum Genet. 2016 Jan;24(1):99-105. doi: 10.1038/ejhg.2015.72. Epub 2015 Apr 15.

  PMID: 25873010 RESULT

MeSH Terms

Conditions

Neoplasms; Colonic Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Thierry FREBOURG, Pr

  University Hospital, Rouen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2010
• First Posted: January 28, 2010
• Study Start: January 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

FR (16)