Abstract
Simple SummaryColorectal cancer (CRC) screening participants with significant traces of hemoglobin in their stool have been reported to have higher mortality and different causes of death (other than CRC) compared to those without. We aimed to investigate these differences among screening participants after 33 years of follow-up. We confirmed that participants with detectable fecal hemoglobin were more likely to die in the study period and to die from different causes, such as cardiovascular and endocrine and hematological diseases, compared to those without detectable fecal hemoglobin. This confirms that fecal hemoglobin may have potential as a marker for diseases not directly related to the colon and rectum and may represent a target for future preventive measures.Fecal hemoglobin (f-Hb) detected by the guaiac fecal occult blood test (gFOBT) may be associated with mortality and cause of death in colorectal cancer (CRC) screening participants. We investigated this association in a randomly selected population of 20,694 participants followed for 33 years. We followed participants from the start of the Hemoccult-II CRC trial in 1985–1986 until December 2018. Data on mortality, cause of death and covariates were retrieved using Danish national registers. We conducted multivariable Cox regressions with time-varying exposure, reporting results as crude and adjusted hazard ratios (aHRs). We identified 1766 patients with at least one positive gFOBT, 946 of whom died in the study period. Most gFOBT-positive participants (93.23%) died of diseases unrelated to CRC and showed higher non-CRC mortality than gFOBT-negative participants (aHR: 1.20, 95% CI 1.10–1.30). Positive gFOBT participants displayed a modest increase in all-cause (aHR: 1.28, 95% CI: 1.18–1.38), CRC (aHR: 4.07, 95% CI: 3.00–5.56), cardiovascular (aHR: 1.22, 95% CI: 1.07–1.39) and endocrine and hematological mortality (aHR: 1.58, 95% CI: 1.19–2.10). In conclusion, we observed an association between positive gFOBT, cause of death and mortality. The presence of f-Hb in the gFOBT might indicate the presence of systemic diseases.
Highlights
Testing for fecal hemoglobin (f-Hb) in average-risk individuals is an integral part of colorectal cancer (CRC) screening programs [1,2]
Since participants could participate in up to nine rounds of screening and have more than one positive guaiac fecal occult blood test (gFOBT) during the trial, we found it necessary to account for differences in the accumulated levels of exposure of each participant by introducing gFOBT results as a time-varying exposure
1766 (8.5%) gFOBTpositive participants were included in the analysis, representing a total of 1866 positive gFOBTs
Summary
Testing for fecal hemoglobin (f-Hb) in average-risk individuals is an integral part of colorectal cancer (CRC) screening programs [1,2]. A recent study found that screening participants with a positive gFOBT had higher all-cause mortality rates and were more likely to die from causes other than CRC compared to those with a negative test. This association persisted after adjusting for possible confounding factors, such as age, sex and social deprivation [11]. A Taiwanese research group conducted a similar study among screening participants investigated with the FIT and their risk of cardiovascular disease and found an increase in incidence and mortality rates as FIT levels increased [12]
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