Charles Cock1, Shahzaib Anwar1, Susan E Byrne2, Rosie Meng3, Susanne Pedersen4, Robert J L Fraser1,2, Graeme P Young2, Erin L Symonds5,6. 1. Department of Gastroenterology and Hepatology, Flinders Medical Centre and College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia. 2. Flinders Centre for Innovation in Cancer (FCIC), College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia. 3. Flinders Centre for Epidemiology and Biostatistics, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia. 4. Clinical Genomics Pty Ltd, North Ryde, NSW, Australia. 5. Flinders Centre for Innovation in Cancer (FCIC), College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia. Erin.Symonds@sa.gov.au. 6. Bowel Health Service, Flinders Medical Centre, Bedford Park, SA, 5042, Australia. Erin.Symonds@sa.gov.au.
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.
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.
Authors: David A Lieberman; Douglas K Rex; Sidney J Winawer; Francis M Giardiello; David A Johnson; Theodore R Levin Journal: Gastroenterology Date: 2012-07-03 Impact factor: 22.682
Authors: Aafke H C van Roon; Janneke A Wilschut; Lieke Hol; Marjolein van Ballegooijen; Jacqueline C I Y Reijerink; Hans 't Mannetje; Laura J C Kranenburg; Katharina Biermann; Anneke J van Vuuren; Jan Francke; Alexandra C M van der Togt; Dik J F Habbema; Monique E van Leerdam; Ernst J Kuipers Journal: Clin Gastroenterol Hepatol Date: 2010-12-23 Impact factor: 11.382
Authors: Joanne M Lane; Elizabeth Chow; Graeme P Young; Norm Good; Alicia Smith; Jeff Bull; Jayne Sandford; Joylene Morcom; Peter A Bampton; Stephen R Cole Journal: Gastroenterology Date: 2010-08-16 Impact factor: 22.682
Authors: T Kambara; L A Simms; V L J Whitehall; K J Spring; C V A Wynter; M D Walsh; M A Barker; S Arnold; A McGivern; N Matsubara; N Tanaka; T Higuchi; J Young; J R Jass; B A Leggett Journal: Gut Date: 2004-08 Impact factor: 23.059
Authors: Jayne Digby; Callum G Fraser; Francis A Carey; Paula J McDonald; Judith A Strachan; Robert H Diament; Margaret Balsitis; Robert J C Steele Journal: J Clin Pathol Date: 2013-02-15 Impact factor: 3.411
Authors: Timothy J H Lathlean; Molla M Wassie; Jean M Winter; Rishabh Goyal; Graeme P Young; Erin L Symonds Journal: BMJ Open Date: 2022-05-30 Impact factor: 3.006
Authors: Berbel Ykema; Lisanne Rigter; Manon Spaander; Leon Moons; Tanya Bisseling; Berthe Aleman; Jan Paul de Boer; Pieternella Lugtenburg; Cecile Janus; Eefke Petersen; Judith Roesink; John Raemaekers; Richard van der Maazen; Iris Lansdorp-Vogelaar; Andrea Gini; Wieke Verbeek; Margriet Lemmens; Gerrit Meijer; Flora van Leeuwen; Petur Snaebjornsson; Beatriz Carvalho; Monique van Leerdam Journal: J Clin Med Date: 2020-01-10 Impact factor: 4.241
Authors: Loretta De Chiara; Leticia Barcia-Castro; María Gallardo-Gómez; María Páez de la Cadena; Vicenta S Martínez-Zorzano; Francisco J Rodríguez-Berrocal; Luis Bujanda; Ane Etxart; Antoni Castells; Francesc Balaguer; Rodrigo Jover; Joaquín Cubiella; Oscar J Cordero Journal: Cancers (Basel) Date: 2022-09-20 Impact factor: 6.575