Clinical trial NCT02542670: Genetic Variants of Selected Genes in Colo-Rectal Cancer Patients.
Official title: Genetic Variants of Selected Genes Using Target Deep Sequencing in Colo-Rectal Cancer Patients.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cancer Colon
Lead sponsor: Tanta University
Sponsor class: OTHER
Collaborators: name: Tanta University
First posted: 2015-09-07
Enrollment: 50
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cancer colon with no distant metastasis Cancer colon with distant metastases control group

Brief summary: Colorectal cancers (CRC) are the third most common human malignancy, and are also the leading cause of cancer related deaths worldwide. Early detection of premalignant lesions such as adenomatous polyps has decreased the risk of CRCs; however, cases which are initially undetected and progress to advanced CRC with distant metastasis are still unfortunately incurable. The development of CRC is a complex and heterogeneous process arising from an interaction between multiple etiological factors, including genetic factors and environmental factors such as diet and lifestyle. The challenges are to understand the molecular basis of individual susceptibility to colorectal cancer and to determine factors that initiate the development of the tumor, drive its progression, and determine its responsiveness or resistance to antitumor agents. Next generation sequencing(NGS)-driven genomic studies are already reporting novel features of cancer genomes beyond the traditional mutational categories. Recent advance in sequencing technology has enabled comprehensive profiling of genetic alterations in CRC.These methods are facilitating an increase in the efficiency and resolution of detection of each of the principal types of somatic cancer genome alterations, including nucleotide substitutions, small insertions and deletions, copy number alterations, chromosomal rearrangements,DNA methylation sequencing such as bisulfite-sequencing and microbial infections. Besides the microsatellite instability (MSI), some researchers reported novel mitochondrial mutations in the cancer genomes. NGS technology will help the investigators for understanding of entire CRC genomes and the obtained knowledge will lead to a better diagnosis and personalized targeted therapeutics for CRC management

Detailed description: Identification of the problem:Colorectal cancers (CRC) are the third most common human malignancy, and are also the leading cause of cancer related deaths worldwide. Early detection of premalignant lesions such as adenomatous polyps has decreased the risk of CRCs; however, cases which are initially undetected and progress to advanced CRC with distant metastasis are still unfortunately incurable. The development of CRC is a complex and heterogeneous process arising from an interaction between multiple etiological factors, including genetic factors and environmental factors such as diet and lifestyle. The challenges are to understand the molecular basis of individual susceptibility to colorectal cancer and to determine factors that initiate the development of the tumor, drive its progression, and determine its responsiveness or resistance to antitumor agents. Next generation sequencing(NGS)-driven genomic studies are already reporting novel features of cancer genomes beyond the traditional mutational categories. Recent advance in sequencing technology has enabled comprehensive profiling of genetic alterations in CRC.These methods are facilitating an increase in the efficiency and resolution of detection of each of the principal types of somatic cancer genome alterations, including nucleotide substitutions, small insertions and deletions, copy number alterations, chromosomal rearrangements,DNA methylation sequencing such as bisulfite-sequencing and microbial infections. Besides the microsatellite instability (MSI), some researchers reported novel mitochondrial mutations in the cancer genomes.NGS technology will help the investigators for understanding of entire CRC genomes and the obtained knowledge will lead to a better diagnosis and personalized targeted therapeutics for CRC management.Experimental design: The study design to attempt to identify the unique mutational spectrum and novel targets of genomic, epigenetic alterations in Egyptian colorectal cancer patients in Delta Regionusing Whole Exome and Epigenetic deep sequencing.Expected results:NGS-based genome analysis facilitates the identification of unrecognized gene mutation of Egyptian CRC cancer especially in Delta Region which may be biologically different from Western CRC as the environmental factors are different.Significance of the expected results:The results of this project will benefit in(1) Identification of novel features or mutation types in CRC genomes In Delta Region. (2) Understanding the advancement of pathway-level in colorectal carcinogenesis and (3) Identify Clinically relevant genetic and epigenetic biomarkers for noninvasive diagnosis and clinically actionable targets for personalized targeted medicine.

Eligibility criteria: Inclusion Criteria:

1. Ages Eligible for Study: 10 Years and older
2. Genders Eligible for Study: Both
3. Patients who can give informed consent themselves
4. 10 healthy controls will also be included in the study.

Exclusion Criteria:

1. Other cancer types rather than CRC.
2. Younger age than 10 years

Primary outcomes:
measure: Number of cancer patients with abnormal genetic mutations .
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Sherief Abd-Elsalam
city: Cairo
country: Egypt
facility: Tanta university hospital
Study officials:
affiliation: Prof of clincal pathology and genetics
name: Said Hammad abdou, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: lecturer of gastroenterology and hepatology
name: Samah mosaad aboelenein, lecturer
role: STUDY_DIRECTOR
affiliation: Prof of gastroenterology and hepatology
name: Asem Elfert, Prof
role: STUDY_CHAIR
affiliation: lecturer of gastroenterology and hepatology
name: Sherief Abd-Elsalam, Lecturer
role: STUDY_CHAIR
affiliation: lecturer of gastroenterology and hepatology
name: Walaa Elkhalawany, Lecturer
role: STUDY_CHAIR
affiliation: Prof of oncology
name: Nehal Elmashad, Prof
role: STUDY_CHAIR
affiliation: Prof of immunology and genetics
name: Mohamed Labib Salem, Prof
role: STUDY_CHAIR
affiliation: lecturer of immunology and genetics
name: Abdel-Aziz Zidan, lecturer
role: STUDY_CHAIR
affiliation: Lecturer of clinical pathology
name: Amira youssef, lecturer
role: STUDY_CHAIR
affiliation: Prof of pathology
name: Ayman Elsaka, prof
role: STUDY_CHAIR
affiliation: Prof of general surgery
name: Gamal Mousa, prof
role: STUDY_CHAIR
affiliation: Prof of public health and medical statistics
name: Khalil Abas, Prof
role: STUDY_CHAIR
affiliation: Prof of general surgery
name: Osama Elkhadrawy, Prof
role: STUDY_CHAIR
affiliation: Tanta University
name: Eman Ebrahim Ebrahim Farghal, Ph.D.
role: STUDY_CHAIR
affiliation: Tanta University
name: Marwa H Saied, Ph.D.
role: STUDY_CHAIR
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