Open Access Study protocol

A prospective study to assess the value of MMP-9 in improving the appropriateness of urgent referrals for colorectal cancer

Angela V Ryan1, Sue Wilson1*, Michael JO Wakelam2, Sally A Warmington1, Janet A Dunn3, Richard FD Hobbs1, Ashley Martin2 and Tariq Ismail4

Author Affiliations

1 Department of Primary Care and General Practice, University of Birmingham, Birmingham B15 2TT, UK

2 Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, UK

3 Health Sciences Research Institute, University of Warwick, Gibbett Hill Campus, Coventry CV4 7AL, UK

4 University Hospital Birmingham Foundation NHS Trust, Queen Elizabeth Hospital, Birmingham B15 2TH, UK

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BMC Cancer 2006, 6:251  doi:10.1186/1471-2407-6-251

Published: 23 October 2006



Bowel cancer is common and is a major cause of death. Most people with bowel symptoms who meet the criteria for urgent referral to secondary care will not be found to have bowel cancer, and some people who are found to have cancer will have been referred routinely rather than urgently. If general practitioners could better identify people who were likely to have bowel cancer or conditions that may lead to bowel cancer, the pressure on hospital clinics may be reduced, enabling these patients to be seen more quickly. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9) have been found to be associated with such conditions, and this can be measured from a blood sample. This study aims to find out whether measuring MMP-9 levels could improve the appropriateness of urgent referrals for patients with bowel symptoms.


People aged 18 years or older referred to a colorectal clinic will be asked to complete a questionnaire about symptoms, recent injuries or chronic illnesses (these can increase the level of matrix metalloproteinases) and family history of bowel cancer. A blood sample will be taken from people who consent to take part to assess MMP-9 levels, and the results of examination at the clinic and/or investigations arising from the clinic visit will be collected from hospital records. The accuracy of MMP-9 will be assessed by comparing the MMP-9 level with the resulting diagnosis. The combination of factors (e.g. symptoms and MMP-9 level) that best predict a diagnosis of malignancy (invasive disease or polyps) will be determined.


Although guidelines are in place to facilitate referrals to colorectal clinics, symptoms alone do not adequately distinguish people with malignancy from people with benign conditions. This study will establish whether MMP-9 could assist this process. If this were the case, measurement of MMP-9 levels could be used by general practitioners to assist in the identification of people who were most likely to have bowel cancer or conditions that may lead to bowel cancer, and who should, therefore, be referred most urgently to secondary care.