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Biomarker
Discovery in Colorectal Cancer
PI: Frank Murray
Project: Colorectal
Cancer is the most common cancer and the second most common cause of
cancer death in Ireland.
Current screening methods are inadequate and expensive. In colorectal
cancer there is a sequential transition through clinical stages of the
disease that is paralleled by a series of well-characterised
alterations in proto-oncogenes and tumour suppressor genes. In colon
cancer activation of mutant K-ras and subsequent inactivation/loss of
p53 are key changes, which drive many interrelated aspects of the
malignant phenotype including mitogenesis and survival. Moreover, both
of these genetic alterations lead to an aberrant phenotype with altered
protein expression. Thus the sequential development of colorectal
cancer provides a rationale to detect a humoral response in different
clinical stages.
Each year in Ireland
there are 1,730 new cases and 925 deaths from colon cancer. The
incidence is between 10-13% of all cancers in Western civilisation. The
two main screening methods, colonoscopy and faecal occult blood testing
are imperfect, expensive and not generally applicable across the
population as a whole. Furthermore our preliminary data on patients
presenting to hospital suggests a significant delay from symptom onset
to presentation to hospital. The early stages of colon cancer are
respectable and surgery is curative. This provides a strong rationale
for an early diagnosis. There are sequential changes in the evolution
of colon cancer and changes in protein expression such as carcinoma
embryonic antigen and cyclooxygenase-2 expression. We will characterise
the humoral response in patients with benign colonic polyps, Crohn’s
disease and ulcerative colitis with the aim of identifying a new set of
biomarkers. (Supported by SFI).
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