Identification of candidate genes predisposing to familial colorectal cancer by germline whole exome sequencing
Year: 2019
Type: dissertation
Study design: Observational Study
Abstract: Colorectal cancer (CRC) is the third most common cause of cancer-related death worldwide.Approximately 5% of CRC is attributable to an inherited high-penetrance pathogenic variant in a known CRC-predisposing gene, often associated with a family history of CRC, a young onset of CRC and/or colonic polyposis.Identification of an inherited genetic variant predisposing to CRC in an individual with CRC enables predictive testing in bloo d relatives, and implementation of risk reduction strategies for individuals with the causative variant within the family.In individuals with familial or young onset CRCs/colonic polyposis in whom a causative germline variant in a known CRC-predisposing gene has not been identified, it is hypothesised that novel CRC-predisposing genes harbouring rare high risk germline variants remain to be discovered.Germline whole exome sequencing (WES) offered a novel and comprehensive approach to identifying potential pathogenic variants in candidate CRC-predisposing genes.This thesis used WES of germline DNA in individuals with unexplained CRC and a high a priori risk of an inherited predisposition to CRC, to prioritise candidate CRC-predisposing genes that were subsequently re-sequenced in a validation cohort of young-onset CRC cases. PrefaceThis thesis involved several collaborations, and due acknowledgement is given throughout this thesis.I would like to thank the familial cancer clinics across Australia who provided clinical samples, and the families who agreed to participate in the study.
Author: Mei Sim Lung
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3026171265