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Title: Improving the sensitivity and specificity of faecal tests for colorectal cancer screening
Author: Hunt, Johanna C.
ISNI:       0000 0001 3584 5431
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2007
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Colorectal cancer (CRC) kills approximately 529,000 people each year. Most CRCs develop from adenomatous polyps that can be detected during screening and removed at the pre-invasive stage of the disease. Screening strategies that detect early stage cancers can reduce morbidity and mortality, and the detection of premalignant polyps can reduce the incidence of CRC. However, none of the currently available screening tests meet all of the criteria of the ideal screening test. Due to its non-invasive and acceptability to the general population, an improved faecal-based test appears to be the way forward. The aim of this study was to improve the sensitivity and specificity of faecal tests for CRC screening. Faecal DNA was extracted from colonoscopy fluid taken from CRC and non-CRC patients during colonoscopy. Mutations of p53 and APC were investigated using amplification of faecal DNA by PCR and subsequent dHPLC analysis. MSI, LOH and mutations in K-ras were assessed using PCR and fragment analysis. The levels of MMP-2 were determined using ELISA. The level of MMP-2 in faecal samples was used to create a model for predicting the CRC status of patients, which had a sensitivity and specificity of 83%. The combined sensitivity and specificity of the faecal assays for the molecular markers was between 65%-71% and 89%-99%, respectively. These results are inline with the majority of previous multiple-marker faecal studies. Furthermore the sensitivity is above that reported for a study of non-rehydrated haemoccult FOBT versus colonoscopy. The use of the assays developed in this study for detecting alterations in the 5 molecular markers have the potential of being more effective in screening for CRC than FOBT. The faecal MMP-2 ELISA could also represent a feasible alternative to FOBT, which could be used in conjunction with the molecular assays.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available