scholarly journals Screening for Colorectal Cancer Leading into a New Decade: The “Roaring ‘20s” for Epigenetic Biomarkers?

2021 ◽  
Vol 28 (6) ◽  
pp. 4874-4893
Author(s):  
Hélder Almeida-Lousada ◽  
André Mestre ◽  
Sara Ramalhete ◽  
Aryeh J. Price ◽  
Ramon Andrade de Mello ◽  
...  

Colorectal cancer (CRC) has an important bearing (top five) on cancer incidence and mortality in the world. The etiology of sporadic CRC is related to the accumulation of genetic and epigenetic alterations that result in the appearance of cancer hallmarks such as abnormal proliferation, evasion of immune destruction, resistance to apoptosis, replicative immortality, and others, contributing to cancer promotion, invasion, and metastasis. It is estimated that, each year, at least four million people are diagnosed with CRC in the world. Depending on CRC staging at diagnosis, many of these patients die, as CRC is in the top four causes of cancer death in the world. New and improved screening tests for CRC are needed to detect the disease at an early stage and adopt patient management strategies to decrease the death toll. The three pillars of CRC screening are endoscopy, radiological imaging, and molecular assays. Endoscopic procedures comprise traditional colonoscopy, and more recently, capsule-based endoscopy. The main imaging modality remains Computed Tomography (CT) of the colon. Molecular approaches continue to grow in the diversity of biomarkers and the sophistication of the technologies deployed to detect them. What started with simple fecal occult blood tests has expanded to an armamentarium, including mutation detection and identification of aberrant epigenetic signatures known to be oncogenic. Biomarker-based screening methods have critical advantages and are likely to eclipse the classical modalities of imaging and endoscopy in the future. For example, imaging methods are costly and require highly specialized medical personnel. In the case of endoscopy, their invasiveness limits compliance from large swaths of the population, especially those with average CRC risk. Beyond mere discomfort and fear, there are legitimate iatrogenic concerns associated with endoscopy. The risks of perforation and infection make endoscopy best suited for a confirmatory role in cases where there are positive results from other diagnostic tests. Biomarker-based screening methods are largely non-invasive and are growing in scope. Epigenetic biomarkers, in particular, can be detected in feces and blood, are less invasive to the average-risk patient, detect early-stage CRC, and have a demonstrably superior patient follow-up. Given the heterogeneity of CRC as it evolves, optimal screening may require a battery of blood and stool tests, where each can leverage different pathways perturbed during carcinogenesis. What follows is a comprehensive, systematic review of the literature pertaining to the screening and diagnostic protocols used in CRC. Relevant articles were retrieved from the PubMed database using keywords including: “Screening”, “Diagnosis”, and “Biomarkers for CRC”. American and European clinical trials in progress were included as well

Author(s):  
Allegra Ferrari ◽  
Isabelle Neefs ◽  
Sarah Hoeck ◽  
Marc Peeters ◽  
Guido Van Hal

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring.In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63-100%, 90-95%, 47-97%, respectively) while minimizing stress and discomfort for the patient.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Justin L. Sovich ◽  
Zachary Sartor ◽  
Subhasis Misra

Background.Worldwide, colorectal cancer (CRC) is the third most common cancer in men and second most common in women. It is the fourth most common cause of cancer mortality. In the United States, CRC is the third most common cause of cancer and second most common cause of cancer mortality. Incidence and mortality rates have steadily fallen, primarily due to widespread screening.Methods.We conducted keyword searches on PubMed in four categories of CRC screening: stool, endoscopic, radiologic, and serum, as well as news searches in Medscape and Google News.Results.Colonoscopy is the gold standard for CRC screening and the most common method in the United States. Technological improvements continue to be made, including the promising “third-eye retroscope.” Fecal occult blood remains widely used, particularly outside the United States. The first at-home screen, a fecal DNA screen, has also recently been approved. Radiological methods are effective but seldom used due to cost and other factors. Serum tests are largely experimental, although at least one is moving closer to market.Conclusions.Colonoscopy is likely to remain the most popular screening modality for the immediate future, although its shortcomings will continue to spur innovation in a variety of modalities.


2019 ◽  
Vol 19 (2) ◽  
pp. 61-66
Author(s):  
Md Rashidul Islam ◽  
Md Shahadot Hossain Sheikh ◽  
Md Abu Taher ◽  
Shima Akter Khatun ◽  
Md Ahsan Habib ◽  
...  

Colorectal cancer, a rising health concern of both east and west , can be prevented and it’s mortality can be reduced by screening all men and women of average risk  at the age of 50 years or older and  at an earlier age for  high risk group of colorectal cancer. Several tests are available for colon cancer screening, including fecal occult blood test (FOBT), flexible sigmoidoscopy, double-contrast barium enema, and colonoscopy. Direct and indirect evidence indicates that all the tests are effective, but they differ in their sensitivity, specificity, cost, and safety. The available evidence does not currently support choosing one test over another. In addition, other new colorectal cancer tests, such as virtual colonoscopy or stool-based molecular testing, have the potential to become important screening tests in the future. Journal of Surgical Sciences (2015) Vol. 19 (2) : 61-66


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 348-348
Author(s):  
Iradj Sobhani ◽  
Roberto Incitti ◽  
Jean-Pierre Roperch

348 Background: Colorectal cancer (CRC) remains a major medical problem in the world. Its early detection impacts the prognosis and the cost of treatment. Fecal occult blood test is a current noninvasive screening method for CRC detection in asymptomatic average risk individuals. It detects less than 50% of cancers and yields a high number of “normal” colonoscopies. The dysregulation of DNA methylation has been recognized as playing a crucial role during CRC development. The aim of the study was to develop a CRC-specific methylated DNA test in serum. Methods: First, the GoldenGate Methylation microarray containing 1,505 CpG loci within 807 cancer-related genes was used to study methylation patterns in CRC patients. We performed such assays on 9 tissues (4 CRC, 4 normal autologous tissues, 1 polyp), 17 blood and urine pooled samples (7 CRC, 6 polyps, 4 normal) and 20 stool samples (7 CRC, 3 polyps, 10 normal). The clinical status of each sample was assessed by colonoscopy and/or pathology findings. Among methylated genes detected in tumour tissue, stools, and blood, NPY, PENK and WIF1 genes were selected taking into account their high degree of methylation. We then carried out a clinical validation by quantitative multiplex methylation-specific PCR (QM-MSP) in two phases: firstly on 30 tissues (15 CRC, 15 homologous normal tissues) and secondly on 193 serum samples (32 CRC, 161 normal). Results: For to obtain the best accuracy of QM-MSP test, we defined for both biological sources a cumulative methylation index (CMI) by adding of the methylation percentage of each gene. At the CMI of 20.0% on tissues, our QM-MSP test allows to diagnose the CRC with the highest accuracy (100% of specificity and 100% of sensitivity). From sera, the CMI has been standardized at 2.0% giving a sensitivity and specificity for detecting CRC of 94.4% and 59.4% respectively (NPV of 92.1% and PPV of 67.8%). Conclusions: We developed a QM-MSP-based analysis of NPY, PENK, and WIF1 methylated genes in serum. This test classified correctly and with a high accuracy the healthy individuals and colon cancer patients. We propose here new sensitive serum-based epigenetic biomarkers as an effective and simple new noninvasive test for CRC screening in the average and high risk populations.


2016 ◽  
Author(s):  
Nielson T. Baxter ◽  
Charles C. Koumpouras ◽  
Mary A.M. Rogers ◽  
Mack T. Ruffin ◽  
Patrick D. Schloss

AbstractBackground:There is a significant demand for colorectal cancer (CRC) screening methods that are noninvasive, inexpensive, and capable of accurately detecting early stage tumors. It has been shown that models based on the gut microbiota can complement the fecal occult blood test and fecal immunochemical test (FIT). However, a barrier to microbiota-based screening is the need to collect and store a patient’s stool sample.Methods:Using stool samples collected from 404 patients we tested whether the residual buffer containing resuspended feces in FIT cartridges could be used in place of intact stool samples.Results:We found that the bacterial DNA isolated from FIT cartridges largely recapitulated the community structure and membership of patients’ stool microbiota and that the abundance of bacteria associated with CRC were conserved. We also found that models for detecting CRC that were generated using bacterial abundances from FIT cartridges were equally predictive as models generated using bacterial abundances from stool.Conclusions:These findings demonstrate the potential for using residual buffer from FIT cartridges in place of stool for microbiota-based screening for CRC. This may reduce the need to collect and process separate stool samples and may facilitate combining FIT and microbiota-based biomarkers into a single test. Additionally, FIT cartridges could constitute a novel data source for studying the role of the microbiome in cancer and other diseases.


Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1820
Author(s):  
Allegra Ferrari ◽  
Isabelle Neefs ◽  
Sarah Hoeck ◽  
Marc Peeters ◽  
Guido Van Hal

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs, which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring. In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques, the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath, and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63–100%, 90–95%, and 47–97%, respectively) while minimizing stress and discomfort for the patient.


2017 ◽  
Vol 32 (4) ◽  
pp. 925-931 ◽  
Author(s):  
Bobbi Jo H. Yarborough ◽  
Ginger C. Hanson ◽  
Nancy A. Perrin ◽  
Scott P. Stumbo ◽  
Carla A. Green

Purpose: Cancer mortality is worse among people with psychiatric disorders. The purpose of this study was to compare facilitators and rates of colorectal cancer (CRC) screening between people with and without mental illnesses. Design: We conducted a secondary analysis using data from a general population cohort study (N = 92 445) that assessed effects of 2 types of CRC screening test kits—guaiac fecal occult blood testing (gFOBT) and fecal immunochemical testing (FIT)—on CRC screening completion. Setting: The setting was a health system that served approximately 485 000 members in urban and suburban Oregon and Washington. Participants: Participants were health system members, categorized by mental illness diagnosis (psychotic disorders, non-psychotic unipolar depression, and no mental illness), who were age-eligible, at average risk of CRC, and were at least 366 days past their last gFOBT with no evidence of other CRC screening. Measures: The outcome was time until completion of CRC screening. Analysis: We used Cox proportional hazard models. Results: FIT reduced CRC screening barriers for all the groups. Compared to people without mental illness diagnoses, those with psychotic disorders were equally likely to screen using FIT (hazard ratio [HR] = .95, p = .679) and those with depression were more likely (HR = 1.17, p = .006). Conclusions: FIT can improve CRC screening rates among people with mental illnesses, particularly depression.


Author(s):  
Brian A. Costello

Colorectal cancer is diagnosed in approximately 137,000 Americans annually and causes 50,000 deaths each year. It is the third most common cause of cancer death in North America and Europe. The incidence of colorectal cancer has decreased since the early 2000s, after it peaked in the late 1990s. The decrease in colon cancer incidence and mortality is attributed to improved screening methods, consisting mainly of endoscopic surveillance. Screening colonoscopies should be initiated by age 50 years for persons with average risk.


2013 ◽  
Vol 27 (4) ◽  
pp. 224-228 ◽  
Author(s):  
Desmond Leddin ◽  
Robert Enns ◽  
Robert Hilsden ◽  
Carlo A Fallone ◽  
Linda Rabeneck ◽  
...  

BACKGROUND: Differences between American (United States [US]) and European guidelines for colonoscopy surveillance may create confusion for the practicing clinician. Under- or overutilization of surveillance colonoscopy can impact patient care.METHODS: The Canadian Association of Gastroenterology (CAG) convened a working group (CAG-WG) to review available guidelines and provide unified guidance to Canadian clinicians regarding appropriate follow-up for colorectal cancer (CRC) surveillance after index colonoscopy. A literature search was conducted for relevant data that postdated the published guidelines.RESULTS: The CAG-WG chose the 2012 US Multi-Society Task Force (MSTF) on Colorectal Cancer to serve as the basis for the Canadian position, primarily because the US approach was the simplest and comprehensively addressed the issue of serrated polyps. Aspects of other guidelines were incorporated where relevant. The CAG-WG recommendations differed from the US MSTF guidelines in three main areas: patients with negative index colonoscopy should be followed-up at 10 years using any of the appropriate screening tests, including colonos-copy, for average-risk individuals; among patients with >10 adenomas, a one-year interval for subsequent colonoscopy is recommended; and for long-term follow-up, patients with low-risk adenomas on both the index and first follow-up procedures can undergo second follow-up colonos-copy at an interval of five to 10 years.DISCUSSION: The CAG-WG adapted the US MSTF guidelines for colonoscopy surveillance to the Canadian health care environment with a few modifications. It is anticipated that the present article will provide unified guidance that will enhance physician acceptance and encourage appropriate utilization of recommended surveillance intervals.


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