scholarly journals Stool DNA Test Targeting Methylated Syndecan-2 (SDC2) as a Noninvasive Screening Method for Colorectal Cancer

2021 ◽  
Author(s):  
Wei-Chih Su ◽  
Wei-Yu Kao ◽  
Tsung-Kun Chang ◽  
Hsiang-Lin Tsai ◽  
Ching-Wen Huang ◽  
...  

Despite the steadily increasing worldwide incidence of colorectal cancer (CRC), an effective noninvasive approach for early detection of CRC is still under investigation. The guaiac-based fecal occult blood test (FOBT) and fecal immunochemical test (FIT) have gained popularity as noninvasive CRC screening tests owing to their convenience and relatively low costs. However, the FOBT and FIT have limited sensitivity and specificity. To develop a noninvasive tool for the detection of CRC, we investigated the sensitivity, specificity, and accuracy of a stool DNA test targeting methylated syndecan-2 (SDC2), which is frequently methylated in patients with CRC. This study enrolled 62 patients diagnosed as having stage 0–IV CRC and 76 healthy participants between July 2018 and June 2019 from two institutions. Approximately 4.5g of stool sample was collected from each participant for detection of human methylated SDC2 gene. In total, 48 of 62 (77.4%) patients with CRC showed positive results, whereas 67 out of 76 (88.2%) healthy participants showed negative results. The area under the curve of the receiver operating characteristic curve constructed was 0.872 for discrimination between patients with CRC and healthy individuals. This study highlights the potential of the fecal methylated SDC2 test as a noninvasive detection method for CRC screening with a relatively favorable sensitivity of 77.4%, a specificity of 88.2% and a positive predictive value of 84.2% compared to other available fecal tests. Further multicenter clinical trials comprising subjects of varied ethnicities are required to validate this test for the mass screening of patients with CRC.

2008 ◽  
Vol 22 (7) ◽  
pp. 631-633 ◽  
Author(s):  
Suzanne Richter

Colorectal cancer (CRC) is the third most common type of cancer diagnosed in Canada, and is the leading cause of cancer-related deaths in nonsmokers. Although CRC is considered to be 90% curable if detected early, the majority of patients present with advanced stage III or IV disease. An effective screening test may significantly decrease disease burden. The present paper examines the rationale and potential of fecal DNA testing as an alternative and adjunct to other CRC screening tests. The most efficacious fecal DNA test developed to date has a sensitivity and specificity of 87.5% and 82%, respectively. The approach has a higher positive predictive value than the currently used fecal occult blood test and offers a noninvasive option to patients. It is not reliant on the presence of bleeding, which may be intermittent or altogether absent. The test is now commercially available and is supported by a number of American insurers. Current challenges include cost reduction and demonstration of mortality benefit in a rigorous clinical trial. Despite current challenges, fecal DNA testing is worth pursuing. Both the American Gastroenterological Society and the American Cancer Society maintain that molecular testing is in its infancy but is promising. Fecal DNA testing has the potential to be an exciting addition to the current armament of CRC screening options.


Author(s):  
G. M. Butrovich ◽  
E. D. Mirlina ◽  
I. G. Habarova ◽  
O. A. Vostrukhina

Colorectal cancer (CRC) is still one of the leading causes of cancer-related death all over the world. An early diagnosis is fundamental thing for reducing the CRC-related morbidity and mortality. Nowadays researchers are studying more reliable and effective non-invasive screening tests, using easily available biological samples, such as feces. Such methods have high potential to collect and deliver samples. The comparison of some new variants genomic fecal DNA analysis and traditional fecal occult blood tests are discussed in this review. Sensitivity, specificity of the methods, processability, efficacy and ability of early CRC screening are the criteria for the preference of the using of one of these methods. These factors give the opportunity to carry out the large-scale CRC screening. This technological advance promises to increase the efficiency of the fecal DNA analysis and put the using of new clinical applications.


2020 ◽  
Vol 20 (2) ◽  
pp. 1193-1200
Author(s):  
Cuiping Yang ◽  
Wei Wu ◽  
Yanping Yang ◽  
Xiaojin Yang ◽  
Jing Sun ◽  
...  

Author(s):  
Lesley-Ann Miller-Wilson ◽  
Lila J Finney Rutten ◽  
Jack Van Thomme ◽  
A Burak Ozbay ◽  
Paul J Limburg

Abstract Purpose Colorectal cancer (CRC) is the second most deadly cancer in the USA. Early detection can improve CRC outcomes, but recent national screening rates (62%) remain below the 80% goal set by the National Colorectal Cancer Roundtable. Multiple options are endorsed for average-risk CRC screening, including the multi-target stool DNA (mt-sDNA) test. We evaluated cross-sectional mt-sDNA test completion in a population of commercially and Medicare-insured patients. Methods Participants included individuals ages 50 years and older with commercial insurance or Medicare, with a valid mt-sDNA test shipped by Exact Sciences Laboratories LLC between January 1, 2018, and December 31, 2018 (n = 1,420,460). In 2020, we analyzed cross-sectional adherence, as the percent of successfully completed tests within 365 days of shipment date. Results Overall cross-sectional adherence was 66.8%. Adherence was 72.1% in participants with Traditional Medicare, 69.1% in participants with Medicare Advantage, and 61.9% in participants with commercial insurance. Adherence increased with age: 60.8% for ages 50–64, 71.3% for ages 65–75, and 74.7% for ages 76 + years. Participants with mt-sDNA tests ordered by gastroenterologists had a higher adherence rate (78.3%) than those with orders by primary care clinicians (67.2%). Geographically, adherence rates were highest among highly rural patients (70.8%) and ordering providers in the Pacific region (71.4%). Conclusions Data from this large, national sample of insured patients demonstrate high cross-sectional adherence with the mt-sDNA test, supporting its role as an accepted, noninvasive option for average-risk CRC screening. Attributes of mt-sDNA screening, including home-based convenience and accompanying navigation support, likely contributed to high completion rates.


Author(s):  
Bryan J Starkey

Colorectal cancer (CRC) causes 20 000 deaths per annum in the UK alone. Screening has been shown to reduce mortality but debate exists as to which approach to use. Direct visualization of the colorectum has the advantage that it detects lesions most effectively and is required at less frequent intervals, but the procedure is invasive and at present too costly for screening purposes. Faecal occult blood measurement, despite its limitations, is currently the recommended screening method, with follow-up of positive tests by colonoscopy or other visualization techniques. This strategy has been shown to reduce mortality from CRC by about 20% and screening trials directed towards individuals in the over 50 years age group are underway in the UK and elsewhere. Future developments in CRC screening include colorectal visualization by computed colonography - a less-invasive alternative to colonoscopy. Developments in stool analysis are also occurring. Examination of faecal samples for cellular products derived from neoplasms (e.g. calprotectin) may prove more sensitive and specific than faecal occult blood measurements. In addition, detection of altered DNA in faeces is being investigated by molecular biology techniques. Using a multi-target assay panel to detect point mutations and other neoplasia-associated DNA abnormalities may be an effective strategy for CRC screening in the future.


2018 ◽  
Author(s):  
Cathy Eng

Colorectal cancer is the third most common cancer and the second leading cause of cancer death in the United States. Although environmental factors, including diet and lifestyle, clearly play a role in the etiology of colorectal cancer, as many as 25% of patients with colorectal cancer have a family history of the disease, which suggests the involvement of a genetic factor. Inherited colon cancers can be divided into two main types: the well-studied but rare familial adenomatous polyposis (FAP) syndrome, and the increasingly well-characterized, more common hereditary nonpolyposis colorectal cancer (HNPCC, a.k.a. Lynch Syndrome). The prevention, screening, diagnosis, and treatment of cancers of the colon and rectum are covered in this chapter. Figures illustrate various forms of adenomatous polyps, the tumor, node, metastasis (TNM) staging system for colorectal cancer, and the five-year survival rate in patients with colorectal carcinoma. Tables describe risk factors; possible chemopreventive agents; evidence supporting the effectiveness of screening tests; features and usage issues with different fecal occult blood tests; recommendations for early detection, screening, and surveillance for patients at different levels of risk; colorectal cancer staging systems; indicators of poor prognosis; and chemotherapeutic and biologic agents in the treatment of colorectal cancer. This chapter contains 197 references.


2021 ◽  
Vol 6 (1) ◽  
pp. 238146832098497
Author(s):  
Andrea Gini ◽  
Maaike Buskermolen ◽  
Carlo Senore ◽  
Ahti Anttila ◽  
Dominika Novak Mlakar ◽  
...  

Background. Validated microsimulation models have been shown to be useful tools in providing support for colorectal cancer (CRC) screening decisions. Aiming to assist European countries in reducing CRC mortality, we developed and validated three regional models for evaluating CRC screening in Europe. Methods. Microsimulation Screening Analysis–Colon (MISCAN-Colon) model versions for Italy, Slovenia, and Finland were quantified using data from different national institutions. These models were validated against the best available evidence for the effectiveness of screening from their region (when available): the Screening for COlon REctum (SCORE) trial and the Florentine fecal immunochemical test (FIT) screening study for Italy; the Norwegian Colorectal Cancer Prevention (NORCCAP) trial and the guaiac fecal occult blood test (gFOBT) Finnish population-based study for Finland. When published evidence was not available (Slovenia), the model was validated using cancer registry data. Results. Our three models reproduced age-specific CRC incidence rates and stage distributions in the prescreening period. Moreover, the Italian and Finnish models replicated CRC mortality reductions (reasonably) well against the best available evidence. CRC mortality reductions were predicted slightly larger than those observed (except for the Florentine FIT study), but consistently within the corresponding 95% confidence intervals. Conclusions. Our findings corroborate the MISCAN-Colon reliability in supporting decision making on CRC screening. Furthermore, our study provides the model structure for an additional tool (EU-TOPIA CRC evaluation tool: http://miscan.eu-topia.org ) that aims to help policymakers and researchers monitoring or improving CRC screening in Europe.


2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Jill Tinmouth ◽  
Emily T. Vella ◽  
Nancy N. Baxter ◽  
Catherine Dubé ◽  
Michael Gould ◽  
...  

Introduction. The objectives of this systematic review were to evaluate the evidence for different CRC screening tests and to determine the most appropriate ages of initiation and cessation for CRC screening and the most appropriate screening intervals for selected CRC screening tests in people at average risk for CRC.Methods. Electronic databases were searched for studies that addressed the research objectives. Meta-analyses were conducted with clinically homogenous trials. A working group reviewed the evidence to develop conclusions.Results. Thirty RCTs and 29 observational studies were included. Flexible sigmoidoscopy (FS) prevented CRC and led to the largest reduction in CRC mortality with a smaller but significant reduction in CRC mortality with the use of guaiac fecal occult blood tests (gFOBTs). There was insufficient or low quality evidence to support the use of other screening tests, including colonoscopy, as well as changing the ages of initiation and cessation for CRC screening with gFOBTs in Ontario. Either annual or biennial screening using gFOBT reduces CRC-related mortality.Conclusion. The evidentiary base supports the use of FS or FOBT (either annual or biennial) to screen patients at average risk for CRC. This work will guide the development of the provincial CRC screening program.


Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1539
Author(s):  
Yi-Chiao Cheng ◽  
Po-Hsien Wu ◽  
Yen-Ju Chen ◽  
Cing-Han Yang ◽  
Jhen-Li Huang ◽  
...  

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes (ADHFE1, SDC2, and PPP2R5C) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated ADHFE1, SDC2, and PPP2R5C for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.


Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 246
Author(s):  
Lasse Kaalby ◽  
Issam Al-Najami ◽  
Ulrik Deding ◽  
Gabriele Berg-Beckhoff ◽  
Robert J. C. Steele ◽  
...  

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.


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