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Low Sensitivity of Fecal Immunochemical Tests and Blood-Based Markers of DNA Hypermethylation for Detection of Sessile Serrated Adenomas/Polyps

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Abstract

Background

Early detection and removal of precursor lesions reduce colorectal cancer morbidity and mortality. Sessile serrated adenomas/polyps (SSP) are a recognized precursor of cancer, but there are limited studies on whether current screening techniques detect this pathology.

Aims

To investigate the sensitivity of fecal immunochemical tests (FIT) and epigenetic biomarkers in blood for detection of SSP.

Methods

A prospective study offered FIT and a blood test (Colvera for methylated BCAT1 and IKZF1) to adults referred for colonoscopy. Sensitivity of FIT and the blood test were determined for four types of pathology: low-risk conventional adenoma, high-risk adenoma, SSP, and absence of neoplasia. Comparisons were made for FIT positivity at 10 and 20 μg hemoglobin (Hb)/g feces.

Results

One thousand eight hundred and eighty-two subjects completed FIT and underwent colonoscopy. One thousand four hundred and three were also tested for methylated BCAT1/IKZF1. The sensitivity of FIT (20 μg Hb/g feces) for SSP was 16.3%. This was lower than the sensitivity for high-risk adenomas (28.7%, p < 0.05), but no different to that for low-risk adenomas (13.1%) or no neoplasia (8.4%). A positive FIT result for SSP was not associated with demographics, morphology, concurrent pathology or intake of medications that increase bleeding risk. FIT sensitivity for SSP did not significantly increase through lowering the positivity threshold to 10 μg Hb/g feces (20.4%, p > 0.05). Sensitivity of the blood test for SSP was 8.8%, and 26.5% when combined with FIT.

Conclusions

Both FIT and blood-based markers of DNA hypermethylation have low sensitivity for detection of SSP. Further development of sensitive screening tests is warranted.

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Acknowledgment

R Meng was supported by a Grant funded by the financial support of Cancer Council SA’s Beat Cancer Project on behalf of its donors and the State Government of South Australia through the Department of Health together with the support of the Flinders Medical Centre Foundation, its donors and partners.

Funding

This study was funded in part by the National Health and Medical Research Council (APP1006242 and APP1017083) and Clinical Genomics Pty Ltd.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Flinders Medical Centre and College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia

    Charles Cock, Shahzaib Anwar & Robert J. L. Fraser

  2. Flinders Centre for Innovation in Cancer (FCIC), College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia

    Susan E. Byrne, Robert J. L. Fraser, Graeme P. Young & Erin L. Symonds

  3. Flinders Centre for Epidemiology and Biostatistics, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia

    Rosie Meng

  4. Clinical Genomics Pty Ltd, North Ryde, NSW, Australia

    Susanne Pedersen

  5. Bowel Health Service, Flinders Medical Centre, Bedford Park, SA, 5042, Australia

    Erin L. Symonds

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  1. Charles Cock
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Corresponding author

Correspondence to Erin L. Symonds.

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Conflict of interest

Scientists from Clinical Genomics Pty Ltd conducted the blood assays (blinded to all clinical outcomes) and assisted with the writing of the manuscript. Fecal immunochemical tests were provided by Eiken Chemical Company, Tokyo, Japan, but they had no influence on study design, analysis or the decision to submit the manuscript for publication. Author G Young is a paid consultant of Clinical Genomics Pty Ltd. S Pedersen is employed by Clinical Genomics Pty Ltd.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Cock, C., Anwar, S., Byrne, S.E. et al. Low Sensitivity of Fecal Immunochemical Tests and Blood-Based Markers of DNA Hypermethylation for Detection of Sessile Serrated Adenomas/Polyps. Dig Dis Sci 64, 2555–2562 (2019). https://doi.org/10.1007/s10620-019-05569-8

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