Oligogenic Determinism of Colorectal Cancer (DOCC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Rouen
ClinicalTrials.gov Identifier:
NCT01057953
First received: January 27, 2010
Last updated: October 15, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention
Cancer
Genetic: Blood drawn

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Oligogenic Determinism of Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by University Hospital, Rouen:

Primary Outcome Measures:
  • genetic variation assessment [ Time Frame: once ] [ Designated as safety issue: No ]

Enrollment: 1550
Study Start Date: January 2010
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Patient
Blood sample for patient included
Genetic: Blood drawn
Blood drawn for patient

  Eligibility

Ages Eligible for Study:   18 Years to 61 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01057953

Locations
France
Centre François Baclesse
Caen, France, 14000
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
Institut Curie
Paris, France, 75005
Hôpital Européen Georges Pompidou
Paris, France
CHU de Rennes
Rennes, France
Centre Eugène Marquis
Rennes, France, 35000
UHRouen
Rouen, France, 76031
CHU de Saint-Etienne
Saint-Etienne, France
CHU de Toulouse
Toulouse, France
Institut Claudius Regaud
Toulouse, France
Institut Gustave Roussy
Villejuif, France, 94800
Sponsors and Collaborators
University Hospital, Rouen
Investigators
Principal Investigator: Thierry FREBOURG, Pr CHU de Rouen
  More Information

No publications provided

Responsible Party: University Hospital, Rouen
ClinicalTrials.gov Identifier: NCT01057953     History of Changes
Other Study ID Numbers: 2009/082/HP
Study First Received: January 27, 2010
Last Updated: October 15, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Rouen:
Colo-Rectal Cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on August 18, 2014