Clinical trial NCT03208777: Telomeric Abnormalities in Colorectal Diseases by Fluorescent in Situ Hybridization Technique
Official title: Telomeric Abnormalities in Benign and Malignant Colorectal Diseases by Fluorescent in Situ Hybridization Technique
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Tumor Gastric
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2017-07-06
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: all patients with colorectal benign or malignant disease

Brief summary: Colorectal carcinoma is a heterogeneous disease that is caused by the interaction of genetic and environmental factors. colorectal carcinoma encompasses a complex disease with different molecular pathways and biological characteristics arising from a multi-step process that implicates several genetic and epigenetic events . The multi-step genetic model involves the loss of function of tumor suppressor genes, such as adenomatous polyposis coli (APC), Telomeres could be a promising marker due to the fact that their lengths change in the colorectal polyp-carcinoma sequence . Moreover, telomere length (TL) is altered in blood cells in patients with colorectal carcinoma

* These findings could suggest that changes in TL may take place before the development of the tumor .

The two main forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) are characterized by chronic intestinal inflammation and risk of progression to colon cancer. One proposed cause of the latter characteristic is chromosome instability, since the rearrangement of genetic material can lead to activation of oncogenes, loss of tumor suppressor genes and other changes that lead to uncontrolled cell growth. Chromosome instability is particularly associated with UC and has been observed in colon epithelial cells and peripheral blood mononuclear cell. Since genomic instability in peripheral blood mononuclear cells (PBMCs) has been used as a biomarker for global cancer risk in a number of diseases, the latter observation suggests the possibility of a chromosome instability syndrome in UC that could affect all tissues. One possible cause of chromosome instability is telomere dysfunction .

Detailed description: Human chromosomes are capped and stabilized by telomeres, which not only protect them from damage but also have a role in regulating cellular senescence. After reaching a critical length, telomeres experience a double DNA change and cells will eventually enter senescence (replication) or cell death . Telomere length and telomere shortening have been long hypothesized to be a biological marker of aging at the cellular level and a potential mechanism of carcinogenesis. Genomic instability is a critical factor in the initiation and progression of human cancers. One mechanism that underlies genomic instability is loss of telomere function .

fluorescent in situ hybridization is a molecular diagnostic technique that utilizes labeled DNA probes to detect or confirm gene or chromosome abnormalities. fluorescent in situ hybridization is often utilized for both research and diagnosis of hematological malignancies and solid tumors. Conceptually, fluorescent in situ hybridization is a very straightforward technique whereby a DNA probe is hybridized to its complementary sequence on chromosomal preparations previously fixed on microscope slides . fluorescent in situ hybridization is able to detect cells that have chromosomal abnormalities consistent with neoplasia .

There has been a surge of published studies which assessed the association between telomere length and development of colorectal carcinoma. Thus, a meta-analysis addressing colorectal carcinoma and telomere length would be a useful addition to the current information in this area.

Eligibility criteria: Inclusion Criteria:

* Adult age group ˃ 18 years.
* Newly diagnosed cases (no previous treatment).
* No treatment was taken for HCV infection.

Exclusion Criteria:

* age group \< 18 years.
* Patients with malignancy of other type.
* Patients not diagnosed by endoscopy or biopsy (not surely diagnosed).

Primary outcomes:
measure: presence of telomeric abnormalities
timeFrame: one year
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: South Egypt Cancer Institute
name: fatma magdy zidan, residant
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bosman F, Yan P. Molecular pathology of colorectal cancer. Pol J Pathol. 2014 Dec;65(4):257-66. doi: 10.5114/pjp.2014.48094.