Quantitative Fecal Hemoglobin May Predict Colon Cancer Risk

May 17, 2011 — Quantitative fecal hemoglobin concentration at first screening predicts the subsequent risk for incident colorectal cancer, according to the results of a prospective cohort study reported May 17 Online First in Lancet Oncology. "Despite widespread use of the immunochemical faecal occult blood test (iFOBT), little is known about the subsequent risk of developing colorectal neoplasia for participants with negative iFOBT results," write Li-Sheng Chen, PhD, from the School of Oral Hygiene, College of Oral Medicine, Taipei Medical University in Taipei, Taiwan, and colleagues. "We investigated whether the concentration of faecal haemoglobin at the first screen is predictive of the subsequent incidence of colorectal neoplasia in those with a negative screening result." Within the Keelung community-based iFOBT screening program for residents who were aged 40 to 69 years between 2001 and 2007, the investigators used a cutoff fecal hemoglobin concentration of 100 ng/mL to define groups with negative and positive results for additional clinical testing. To identify cases of colorectal cancer, the investigators followed up on 44,324 participants with negative iFOBT results and 1668 with positive iFOBT results at the first screen, including 854 who refused colonoscopy and 814 with a false-positive iFOBT result as determined at colonoscopy. The association between baseline fecal hemoglobin concentration and the risk for incident colorectal cancer was determined after adjustment for possible confounders. During follow-up (median duration, 4.39 years; interquartile range, 2.53 - 6.12), the incidence of colorectal cancer increased from 1.74 per 1000 person-years for those with baseline fecal hemoglobin concentration of 1 to 19 ng/mL, to 7.08 per 1000 person-years for those with a baseline concentration of 80 to 99 ng/mL. Compared with baseline fecal hemoglobin concentration of 1 to 19 ng/mL, adjusted hazard ratios (HRs) increased from 1.43 (95% confidence interval [CI], 1.08 - 1.88) for baseline fecal hemoglobin concentration of 20 to 39 ng/mL, to 3.41 (95% CI, 2.02 - 5.75) for a baseline concentration of 80 - 99 ng/mL (P for trend < .0001). Inclusion of repeated iFOBT measurements did not affect these findings. The risk for incident colorectal cancer was highest for those who initially refused colonoscopy (adjusted HR, 8.46; 95% CI, 6.08 - 11.76). "Quantitative faecal haemoglobin concentration at first screening predicts subsequent risk of incident colorectal neoplasia," the study authors write. "During follow-up, risk stratification based on faecal haemoglobin could help clinicians, with particular attention being paid to those with higher initial faecal haemoglobin concentrations, especially those just under the threshold taken to indicate presence of colorectal neoplasia." Limitations of this study include fecal hemoglobin concentration unknown in 17.3% of the cohort, small number of false-positive cases, and difficulty comparing the findings vs those of previous studies. In an accompanying comment, Callum G. Fraser, from the University of Dundee, Scotland, United Kingdom, notes that these findings have important implications for the design of future screening programs. "Faecal haemoglobin concentration at baseline could provide a means for determining risk; low, intermediate, high-risk, and extremely high-risk groups could be defined, which would allow for individually tailored screening strategies," Dr. Fraser writes. "With modern information technology, flair, and imagination, risk-adapted strategies could be adopted in future screening programmes. New data on associations between faecal haemoglobin concentration and demographic characteristics should also affect programme design." This study has received no funding. The study authors have disclosed no relevant financial relationships. Dr. Fraser has received payment for consultancy work from Immunostics Inc and Alpha Labs Ltd. Lancet Oncol. Published online May 17, 2011. Abstract Extract