The Lothian Bowel Symptoms Study (LABSS)
Research type
Research Study
Full title
The Lothian Bowel Symptoms Study (LABSS); Risk of Significant Colorectal Disease in Symptomatic Patients
IRAS ID
228631
Contact name
Evropi Theodoratou
Contact email
Sponsor organisation
The University of Edinburgh
Duration of Study in the UK
2 years, 11 months, 31 days
Research summary
Summary of Research
Colorectal cancer (CRC) is the 2nd most common cause of cancer death accounting for >16,000 deaths per year in the UK. With this research we aim to improve and refine significant colorectal disease identification. There is a need to identify those with higher risk to prioritise referral times for colonoscopy since most bowel symptoms do not indicate CRC or high risk adenomas (HRAs). In Scotland a colonoscopy crisis has been observed with a recent escalation in primary care referrals (almost quadrupled between 2007 and 2012 - data from NHS Tayside) without a similar escalation in CRC rates (current “conversion” rate to cancer in NHS Lothian is <4% for symptomatic referrals) placing considerable demand on colonoscopy resources. Hence there is substantial potential to inform referral pathways.
The primary objectives and outcomes of this study include:
(i) To recruit 5,000 participants with bowel symptoms from NHS Lothian endoscopy clinics. The participants will complete a short questionnaire, give a blood sample and consent to sharing of clinical data with the research team.
(ii) To construct risk prediction models for significant colorectal disease risk by combining genetic risk variants, novel biomarkers, genetic scores of other markers, family history of cancer, demographic items (such as age and sex), clinical and lifestyle factors.
(iii) To assess the risk prediction models as how well they differentiate those that have serious colorectal disease and those that do not. These risk prediction models could potentially be used in primary care settings to assist in directing endoscopy resources to those who would benefit most.Summary of Results
The Lothian Bowel Symptoms Study (LABSS) – colorectal cancer reduction through risk stratification of screening, follow-up and treatment The study was led by Professor Evi Theodoratou, sponsored by the University of Edinburgh and NHS Lothian Health Board’s Academic and Clinical Central Office for Research and Development (ACCORD) and was funded by Cancer Research UK.
LABSS started in 2017, with recruitment of participants beginning in November of that year. Initially, recruitment took place in the Western General Hospital, Edinburgh. Further study sites opened in 2018-19 in NHS Lothian (The Royal Infirmary Edinburgh), NHS Forth Valley (Forth Valley Royal Hospital) and NHS Lanarkshire (University Hospital Wishaw and University Hospital Monklands). We would like to thank all study participants for giving their consent to participate in the study and their contribution to its outcomes.
Colorectal cancer (CRC) is a malignant tumour growing in the inner lining of the large intestine (caecum, ascending, transverse, descending or sigmoid colon, rectum). Bowel symptoms are common and, in most cases, they are non-serious or self-limiting but a very small proportion of people with bowel symptoms may have a more serious illness.LABSS aim was to improve prediction of people with serious bowel disease and prioritise testing and treatment for these people.
The study objectives were to
• Advance the diagnosis of people more likely to develop a serious bowel disease and help improve outcomes.
• Develop a reliable tool that would identify people more likely to develop a serious bowel disease that would benefit from being referred to colonoscopy earlier.
• Develop a reliable tool that would identify people with no serious conditions for which invasive investigations like colonoscopy would not be necessary.People invited to take part in the study had new bowel symptoms (such as a change in bowel habit, blood in stool, weight loss, abdominal pain, anaemia) and were referred for a colonoscopy = or had a consultation in a colorectal surgery/gastroenterology clinic. A colonoscopy is the standard procedure to examine the lining of the large intestine.
Participants were seen by a research nurse and, once they had consented to take part in the study, they completed a study questionnaire. The questionnaire asked for information on family; medical and medication history. Participants also had to give permission for approved members of the research team to access their medical records, tissue samples and test results. During their meeting with the nurse, participants gave blood (and/or saliva) samples and received a leaflet with information on how to improve their bowel health. The leaflet was created with the help of people with bowel symptoms and highlighted the importance of attending the bowel cancer screening test.
Primarily due to the Covid-19 pandemic, target recruitment numbers were not achieved. However, through collaboration with the Scottish Colorectal Cancer Study (SOCCS3), additional eligible participants were identified and this allowed to recruit enough people with colorectal cancer.
Genetic and vitamin D analyses were completed, as well as cost effectiveness analysis. Unfortunately, data from calcium analysis of samples was not obtained since a type of blood tube was used by mistake that made the calcium results undetectable. There would not have been calcium data for all participants at any rate since blood plasma samples could not be taken after the halt in recruitment due to the Covid-19 pandemic. All regulatory processes relating to this were followed and there was minimal impact on overall study outputs (as set out in the ACCORD report).
Results
People with bowel symptoms who later developed CRC were generally older, more likely to be men, had lower body weight and had a higher genetic risk compared to people who had symptoms but did not develop CRC.
When we examined specific symptoms, we found that more people who developed CRC had anaemia compared to those who stayed healthy, while fewer of them experienced changes in bowel habits, weight loss, or abdominal pain compared to those with symptoms but no CRC. When all symptoms were taken into account, only changes in bowel habits and abdominal pain were found to be predictors of CRC risk. Specifically, people with changes in their bowel habits and those with abdominal pain were significantly less likely to develop CRC.
More importantly, the study found that integrating genetic risk scores with traditional clinical and demographic factors improved CRC prediction and successfully created a tool to help identify which people are more likely to develop CRC based on their bowel symptoms. Including a person's genetic risk in the tool made it even better at identifying those at higher risk, which could help early diagnosis and treatment decisions.
How has this study helped people and researchers?
The study has highlighted which symptoms are most important to watch for when experiencing bowel issues related to CRC. We have also developed an online calculator that both people and clinicians can use to estimate the individual risk of developing CRC. This tool is based on factors such as genetics, age, sex, and symptoms like changes in bowel habits and abdominal pain. This tool, alongside insights from the study, could help doctors identify which people might benefit from a colonoscopy and which people, despite having symptoms, might not need one. This would benefit both people and the NHS by reducing unnecessary tests and saving costs.
For researchers, the study has been highly significant, leading to several research publications that have improved our ability to predict CRC risk based on symptoms and genetic factors.
Details of further research planned
Some further research plan from the team includes further exploration of genetics and gene methylation to see how this influences colorectal cancer risk. We are also doing a systematic review of all the published literature to see how different characteristics may influence the result of a bowel screening test.More about the study
On our website, you can see a list of all the key publications that originated from the fellowship that funded the study:
https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fwww.ed.ac.uk%252Fusher%252Flothian-bowel-symptoms-study%252Fresearch%252Fkey-publications%2FNBTI%2FvQW-AQ%2FAQ%2F66957f88-4519-4ffc-acf7-530a800340b7%2F1%2FLMP25m97HS&data=05%7C02%7Capprovals%40hra.nhs.uk%7Ce0bef4da30d34ef4934808ddcf5de378%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638894724422030946%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=kwS41zNwUUp%2Bccqcze8vt%2FffGV8Ca5KUpo6TacE8%2BPk%3D&reserved=0REC name
South East Scotland REC 01
REC reference
17/SS/0087
Date of REC Opinion
9 Aug 2017
REC opinion
Further Information Favourable Opinion