Individuals with a negative faecal test result at first screen (blood concentrations of less than 100 ng per mL) might be at increased risk of developing colorectal cancer in line with increasing faecal haemoglobin concentration. The findings, published Online First in The Lancet Oncology, suggest that initial faecal haemoglobin concentration could be used to define groups at low, intermediate, and high risk of developing new colorectal neoplasia (abnormal growth of cells), and might encourage some people who avoid repeat screening to be tested.
Immunochemical faecal occult blood testing (iFOBT), which uses antibodies to detect hidden human blood (haemoglobin) in stool, is widely used to screen for colorectal cancer. It is well known that people with faecal haemoglobin concentrations higher than 100 ng per mL are at increased risk of colorectal neoplasia. However, little is known about the subsequent risk of developing colorectal cancer for people who have a negative result (ie, < 100 ng per mL) at the first screen.
In this study, a team from Taiwan led by Hsiu-Hsi Chen from the National Taiwan University, Taipei, Taiwan, examined the association between faecal haemoglobin concentration and risk of subsequent adenoma and colorectal cancers in individuals with negative findings at the first screen. They also calculated the subsequent risk for non-referrals (individuals with faecal haemoglobin concentrations higher than 100 ng/mL who refused colonoscopy) and false-positives (in whom colonoscopy did not find disease).
Between 2001 and 2007, 44 324 participants from the Keelung community-based iFOBT screening programme for residents aged 40 years with negative results at the first screen were followed up to find cases of colorectal neoplasia and modelling was used to calculate the risk of developing neoplasia after controlling for conventional risk factors including age, sex, family history of colorectal cancer, consumption of meat, and body mass index.
Among individuals with negative results, haemoglobin concentration was predictive of neoplasia and subsequent progression to cancer. The higher the initial faecal haemoglobin concentration the greater the likelihood of developing colorectal neoplasia. Non-referrals had the highest risk of colorectal neoplasia and false-positive cases the lowest risk.
The authors suggest that faecal haemoglobin could be used to define groups at low, intermediate, and high risk and tailor screening strategies accordingly.
They say: "Providing such risk stratification for participants with a negative finding at the first screen could enhance awareness among those with higher initial faecal haemoglobin concentration, particularly concentrations just under the usual threshold taken to indicate colorectal neoplasia."
They conclude: "The findings not only confirm the value of using baseline faecal haemoglobin concentration as a measure of subsequent risk of colorectal cancer, but also show that rising faecal haemoglobin concentration is a sign of rising risk of colorectal cancer."
In a Comment, Callum Fraser from the University of Dundee, Scotland, UK says: "There is likely a continuum of risk of colorectal neoplasia as faecal haemoglobin increases from zero." These findings, he adds, have important implications for the design of future screening programmes.
Professor Hsiu-Hsi Chen, College of Public Health, National Taiwan University, Taipei, Taiwan. T) +886 2 33668033 or +886 953196150 E) chenlin@ntu.edu.tw
Professor Callum Fraser, University of Dundee, Scotland, UK. T) +44 (0) 1382 553799 E) callum.fraser@nhs.net
Journal
The Lancet Oncology