Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.823117
Title: Biomarkers and risk stratification in colorectal neoplasia
Author: Pearce, Lyndsay
ISNI:       0000 0005 0289 9045
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2019
Availability of Full Text:
Access from EThOS:
Access from Institution:
Abstract:
Over the last decade there have been considerable advances in the concept of personalising and individualising risk across a number of different cancer groups to identify more effective strategies for disease prevention, screening, treatment and prevention of recurrence. Colorectal cancer (CRC) is a heterogenous disease and the second most common cause of cancer death in the UK. Early detection of disease through the NHS Bowel Cancer Screening Programme (NHS BCSP) enables identification of cancers at an earlier stage with wider ranging treatment options and potentially less risk of recurrent disease. Hereditary colorectal cancer syndromes account for approximately 5% of all colorectal cancers. Lynch Syndrome patients exhibit DNA mismatch repair deficiency and have up to an 80% lifetime risk of colorectal cancer (compared to 5% in the background population) with wide ranging age of onset of disease. This thesis consists of four related studies. The purpose of the research was to conduct a thorough literature review and investigate different aspects relevant to individualisation of risk in patients with or at risk of colorectal cancer. These include; single nucleotide polymorphisms (SNPs) and their role in predicting age of onset of colorectal cancer in patients with Lynch Syndrome (LS); follow up after curative resection for sporadic colorectal cancer; Beta-2 Microglobulin (B2M) mutation status and the impact on prevalence of recurrent disease in patients with MSH2 loss and finally oligopolyposis detection through the NHS BCSP and role of regional genetic centres in the management of these patients. Incidence of oligopolyposis within the bowel cancer screening programme is small (0.79%) but there is a high incidence (50%) of synchronous or high grade dysplasia in these patients. There are no local, regional or national guidelines for the management of patients with oligopolyposis detected through the NHS BCSP. SNPs associated with sporadic CRC were not demonstrated to have a multiplicative effect on age of onset and risk of developing colorectal cancer in patients with MLH1 and MSH2 loss. In sporadic colorectal cancer, a high proportion of patients who develop recurrent colorectal cancer do so in the first three years after surgery (95%) and have surgically treatable disease (36.6%). Intensive CT imaging is demonstrated to be pragmatic in clinical practice. There was no disease recurrence in patients with colorectal cancer, MSH2 loss and B2M mutation. CRC is a heterogenous disease with implications for familial risk and, in some patients, other syndrome specific malignancies. Individualising and stratifying risk is appropriate in high risk and sporadic populations, throughout screening, management and surveillance of the disease within to optimise clinical outcomes for patients.
Supervisor: Evans, Dafydd Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.823117  DOI: Not available
Keywords: Beta-2 Microglobulin ; Follow up after cancer ; Single Nucleotide Polymorphism ; Cancer ; Risk ; Colorectal ; Oligopolyposis
Share: