ABSTRACT: Background and study aims
Genetics aspects of colorectal cancer throughout the world are gaining considerable scientific attention due to their impact on surveillance and management, including targeted therapy. Microsatellites are short tandem repeat DNA sequences distributed throughout the human genome. Secondary to their repeated structure, microsatellites are disposed to errors that are ordinarily fixed by the mismatch repair system (MMR), which when faulty, leads to a strong mutator phenotype known as microsatellite instability (MSI). MSI is one of the major pathways causing colorectal cancer, as it accounts for 15% of all colorectal cancer cases in Caucasian populations.
Several clinical trials have demonstrated that MSI-high colorectal cancer is significantly responsive to immunotherapy using immune checkpoint inhibitors. In Africa, there is a dearth of data on the subject, and in Rwanda specifically, there is presently no reported data on this subject. To our knowledge, this is the largest MSI status study on CRC in an African population.
There are mismatch repair (MMR) genes that are responsible for correcting errors that arise during DNA replication. Proteins within the MMR system are MLH1, PMS2, MSH2, MSH6, MLH3, MSH3, PMS1, and Exo1. When the repair system is ineffective, it results in a strong mutator phenotype called microsatellite instability (MSI). MSI is one of the major carcinogenic (cancer-causing) pathways of colorectal cancer, and there are usually two mechanisms:
1. Hereditary nonpolyposis colorectal cancer, commonly known as Lynch Syndrome, where a mutation in one of the MMR genes is inherited from a parent
2. Sporadic mutation (a mutation that occurs throughout the course of a person's lifetime and is not inherited), which accounts for 15% of colorectal cancers, mostly occurring in the MLH1 gene
Who can participate?
Colorectal cancer patients who have been diagnosed either at King Faisal Hospital (KFH) or at Rwanda Military Hospital (RMH) between 01/01/2019 and 31/12/2021.
What does the study involve?
This study will look at the medical records of all colorectal cancer patients meeting the selection criteria during the study period. Data will be entered directly into a Microsoft Excel data collection tool and stored on a password-protected laptop. Colorectal cancer tissue or blood collected as part of routine medical care will be used for DNA analysis to identify microsatellite instability (MSI). A commercial kit from Promega (MSI Analysis System, Version 1.2) will be used to categorise MSI in one of three categories: MSI-H, MSI-L, or MSS.
