Molecular biomarkers of colorectal carcinogenesis and their role in surveillance and early intervention.
Modern medicine is increasingly focused towards population surveillance for disease, coupled with the implementation of preventative measures applied to 'at-risk' patients. Surveillance in colorectal cancer is limited by the cost and risk of endoscopy. Trials of putative chemopreventive agents in colorectal cancer are hampered by difficulties in following up large cohorts of patients over long periods of time to ascertain the clinical effect. Research into possible pathways of colorectal carcinogenesis has revealed a range of biological intermediates which could be used in surveillance, the identification of high risk populations and early diagnosis of cancer. The aim of this paper was to review the possible role of biomarkers in surveillance and the timing of intervention. A literature review using both Medline and Web of Science was performed from 1995 onwards using keywords: biomarkers, colorectal cancer, carcinogenesis, chemoprevention, surveillance and screening. Research has identified many potential biomarkers, such as cyclooxygenase-2 (COX-2), oxidative DNA adducts and glutathione S-transferase (GST) polymorphisms, which could be applied in a clinical setting to screen for and detect colorectal cancer. Molecular biomarkers, such as COX-2, oxidative DNA adducts and GST polymorphisms offer new prospects in the detection of early colorectal cancer, surveillance of high-risk populations and prediction of the clinical effectiveness of chemopreventive drugs. Their role could be extended into surgical surveillance for potentially operable disease and post-operative follow-up for disease recurrence. Research should be directed at assessing complementary biomarkers to increase clinical effectiveness in determining management options for patients.
Garcea
G
G
University Department of Oncology, 5th floor, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, UK. gg43@le.ac.uk
Sharma
R A
RA
Dennison
A
A
Steward
W P
WP
Gescher
A
A
Berry
D P
DP
D020137:Base Pair Mismatch; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000235:genetics / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D018736:DNA Adducts / Q000032:analysis; D005243:Feces / Q000737:chemistry; D017491:Genes, APC; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D013058:Mass Spectrometry; D008565:Membrane Proteins; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012307:Risk Factors
D014408:Biomarkers, Tumor; D018736:DNA Adducts; D007527:Isoenzymes; D008565:Membrane Proteins; D003577:Cytochrome P-450 Enzyme System; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D005982:Glutathione Transferase