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LRP1 Methylation and Colon Cancer

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ClinicalTrials.gov Identifier: NCT02786602
Recruitment Status : Completed
First Posted : June 1, 2016
Last Update Posted : March 3, 2017
Sponsor:
Information provided by (Responsible Party):
CHU de Reims

Brief Summary:

Colorectal cancer (CRC) is a major public health problem in France and worldwide. CRC is the third most common cancer in incidence and mortality in France. The vast majority of these cancers are adenocarcinomas that arise sporadically and develop from precursor lesions: adenoma. All CRC with the same disease stage do not have the same prognosis. Various parameters have been identified as factors influencing the prognosis and allows adjustment of the treatment. The poor histoprognostic factors are vessels and nerves invasion by the tumor or the mucinous adenocarcinoma subtype. At the molecular level, the presence of microsatellite instability (MSI) improves the prognosis, while the presence of a BRAF mutation is an independent poor prognostic factor.

The different molecular pathways of colonic carcinogenesis are the chromosomal instability pathway, the microsatellite instability pathway inducing errors in DNA mismatch repair and the CpG Island Methylator Phenotype (CIMP). The hypermethylation of CpG islands of genes promoters leads to an over or most frequently under gene expression. CIMP is observed in near 15% of CRC and is associated with specific clinical and pathological features: older patients, female predominance, right colonic involvement, poorly differentiated or mucinous adenocarcinomas. From a molecular point of view, the high CIMP phenotype is strongly associated with the presence of BRAFV600E mutation, the absence of RAS mutation and the presence of microsatellite instability. The prognostic value of CIMP is actually controversial. A recent meta-analysis found that the CIMP phenotype was associated with a poor prognosis. Methylation of some genes promoters as CDKN2A is associated with a poor prognosis.

LRP-1 (low density lipoprotein receptor-related protein 1) is a multifunctional endocytic receptor that belongs to the LDL receptors the family. It mediates the clearance of many extracellular enzymes involved in the spread of cancer cells: metalloproteinases and serine proteinases. Decrease of LRP-1 activity or loss of LRP-1 expression correlates with increased aggressiveness of cancer cells in certain types of cancer. The expression of LRP-1 has almost never been studied in CRC. Only one immunohistochemical study of LRP-1 protein expression in colonic adenocarcinoma has been published to date. This study shows that tumor cells express LRP-1, but in nearly half the cases, weaker than in normal cells colic. The mechanisms involved in the decrease of expression are not known.

An epigenetic mechanism might be involved as hypermethylation of the of LRP-1 gene promoter, especially as the promoter of this gene is rich in CpG islands (methylation targets). Clinical and prognostic significance of the LRP-1 gene expression and promoter methylation is actually unknown.


Condition or disease Intervention/treatment
Colon Cancer Genetic: pyrosequencing

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Study Type : Observational
Actual Enrollment : 345 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Prognostic Impact of the Endocytic Receptor LRP-1 Gene Promoter Methylation in a Retrospective Study of Colonic Adenocarcinomas
Actual Study Start Date : May 2016
Actual Primary Completion Date : November 2016
Actual Study Completion Date : March 2017



Primary Outcome Measures :
  1. Clinical characteristics (age, sex, tumor location) compared between LRP1 high and low methylation groups. [ Time Frame: patients operated between september 2006 and december 2012 ]

Biospecimen Retention:   Samples With DNA
Biobank


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Study Population
Adult patients with sporadic colonic adenocarcinoma treated by surgery at the Academic Hospital of Reims without any neoadjuvant therapy.
Criteria

Inclusion Criteria:

  • Adult patient, with colonic adenocarcinoma treated by surgery, at the Academic hospital of Reims, without neoadjuvant treatment, without familial predisposition for colonic cancer, who gave consent for the present study
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Responsible Party: CHU de Reims
ClinicalTrials.gov Identifier: NCT02786602    
Other Study ID Numbers: PA16046
First Posted: June 1, 2016    Key Record Dates
Last Update Posted: March 3, 2017
Last Verified: March 2017
Additional relevant MeSH terms:
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Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases