Genetic Variants of Selected Genes in Colo-Rectal Cancer Patients.

• ClinicalTrials.gov Identifier: NCT02542670
• Recruitment Status: Unknown
• First Posted: September 7, 2015
• Last Update Posted: July 26, 2017
• Sponsor: Sherief Abd-Elsalam
• Collaborator: Tanta University
• Information provided by (Responsible Party): Sherief Abd-Elsalam, Tanta University

Study Description

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

Condition or disease	Intervention/treatment
Cancer Colon	Genetic: Whole genome sequencing

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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 50 participants
• Observational Model: Case-Control
• Time Perspective: Retrospective
• Official Title: Genetic Variants of Selected Genes Using Target Deep Sequencing in Colo-Rectal Cancer Patients.
• Actual Study Start Date: July 2015
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2019

Groups and Cohorts

Group/Cohort	Intervention/treatment
Cancer colon with no distant metastasis; Genetic: Whole genome Sequencing	Genetic: Whole genome sequencing; At least 50 ng of tumor DNA will be extracted from FFPE samples and/or fresh tissue and used for hybridization capture and NGS using the IlluminaMiSeqDx platform.
Cancer colon with distant metastases; Genetic: Whole genome Sequencing	Genetic: Whole genome sequencing; At least 50 ng of tumor DNA will be extracted from FFPE samples and/or fresh tissue and used for hybridization capture and NGS using the IlluminaMiSeqDx platform.
control group; Genetic: Whole genome Sequencing	Genetic: Whole genome sequencing; At least 50 ng of tumor DNA will be extracted from FFPE samples and/or fresh tissue and used for hybridization capture and NGS using the IlluminaMiSeqDx platform.

Outcome Measures

Primary Outcome Measures :

1. Number of cancer patients with abnormal genetic mutations . [ Time Frame: 2 years ]
   Number of cancer patients having abnormal genetic mutations .

Biospecimen Retention:   Samples With DNA

At least 50 ng of tumor DNA will be extracted from FFPE samples and/or fresh tissue and used for hybridization capture and NGS using the IlluminaMiSeqDx platform.

Eligibility Criteria

• Ages Eligible for Study: 10 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Cancer colon with no distant metastasis Cancer colon with distant metastases control group

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

Contacts and Locations

Contacts

Contact: Sherief Abd-Elsalam, Lecturer; 00201095159522; sherif_tropical@yahoo.com

Locations

Egypt

Sherief Abd-Elsalam; Recruiting

Cairo, Egypt

Contact: Sherief Abd-elsalam, lecturer 00201000040794 Sherif_tropical@yahoo.com

Tanta university hospital; Recruiting

Cairo, Egypt

Contact: Sherief Abd-Elsalam 00201000040794 Sherif_tropical@yahoo.com

Sponsors and Collaborators

Sherief Abd-Elsalam

Tanta University

Investigators

• Principal Investigator: Said Hammad abdou, Prof; Prof of clincal pathology and genetics
• Study Director: Samah mosaad aboelenein, lecturer; lecturer of gastroenterology and hepatology
• Study Chair: Asem Elfert, Prof; Prof of gastroenterology and hepatology
• Study Chair: Sherief Abd-Elsalam, Lecturer; lecturer of gastroenterology and hepatology
• Study Chair: Walaa Elkhalawany, Lecturer; lecturer of gastroenterology and hepatology
• Study Chair: Nehal Elmashad, Prof; Prof of oncology
• Study Chair: Mohamed Labib Salem, Prof; Prof of immunology and genetics
• Study Chair: Abdel-Aziz Zidan, lecturer; lecturer of immunology and genetics
• Study Chair: Amira youssef, lecturer; Lecturer of clinical pathology
• Study Chair: Ayman Elsaka, prof; Prof of pathology
• Study Chair: Gamal Mousa, prof; Prof of general surgery
• Study Chair: Khalil Abas, Prof; Prof of public health and medical statistics
• Study Chair: Osama Elkhadrawy, Prof; Prof of general surgery
• Study Chair: Eman Ebrahim Ebrahim Farghal, Ph.D.; Tanta University
• Study Chair: Marwa H Saied, Ph.D.; Tanta University

More Information

• Responsible Party: Sherief Abd-Elsalam, Lecturer, Tanta University
• ClinicalTrials.gov Identifier: NCT02542670
• Other Study ID Numbers: Dr Said Hammad
• First Posted: September 7, 2015
• Last Update Posted: July 26, 2017
• Last Verified: July 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

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