A new noninvasive blood-test for the early detection of colorectal cancer.

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.

2005 ◽  
Vol 115 (3) ◽  
pp. 493-496 ◽  
Author(s):  
Guy D. Launoy ◽  
Hughes J. Bertrand ◽  
Celia Berchi ◽  
Vincent Y. Talbourdet ◽  
Anne Valérie N. Guizard ◽  
...  

2021 ◽  
pp. 333-341
Author(s):  
Nur-Nadiatul-Asyikin Bujang ◽  
Yu-Jie Lee ◽  
Siti-Anis-Suraya Mohd-Zain ◽  
Junita-Harizon Aris ◽  
Fitri-Amalina Md-Yusoff ◽  
...  

PURPOSE The Malaysian Ministry of Health had launched free opportunistic screening for colorectal cancer using immunochemical fecal occult blood test (iFOBT) targeting the average-risk individuals since 2014. This study aims to determine factors associated with colorectal cancer screening using iFOBT among the average-risk Malaysian population. METHODS A cross-sectional study was conducted at five government-run health clinics in the state of Selangor. Adults with an average risk of colorectal cancer (age > 50 years, asymptomatic, and no family history of colorectal cancer) were recruited using systematic random sampling. An interviewer-administered questionnaire adapted from the Cancer Awareness Measure and Health Belief Model was used. RESULTS The median age of participants was 61 years (interquartile range, 56 to 66). Almost 60% of participants indicated their willingness to be screened. However, only 7.5% had undergone iFOBT. Good knowledge of risk factors of colorectal cancer, perceived susceptibility to the disease, and the doctor's recommendation were associated with increased willingness to be screened: adjusted odds ratio (aOR), 1.66 (95% CI, 1.12 to 2.46); aOR, 1.70 (95% CI, 1.08 to 2.70); and aOR, 5.76 (95% CI, 2.13 to 15.57), respectively. Nevertheless, being elderly (aOR, 0.67; 95% CI, 0.45 to 0.99) and high negative perception toward the testing method (iFOBT) (aOR, 0.12; 95% CI, 0.05 to 0.30) were independently associated with lower willingness to be screened. Multivariable analysis within the average-risk individuals who were willing to be screened for colorectal cancer showed that the doctor’s recommendations remained as an important cue for positive action, whereas negative perception toward the test was a significant barrier to the actual uptake of iFOBT. CONCLUSION The present findings must be factored in when tailoring colorectal cancer screening promotion activities in multiethnic, middle-income settings.


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


2021 ◽  
Author(s):  
Maria Gallardo-Gomez ◽  
Mar Rodriguez-Girondo ◽  
Nuria Planell ◽  
Sebastian Moran ◽  
Luis Bujanda ◽  
...  

Early detection has proven to be the most effective strategy to reduce the incidence and mortality of colorectal cancer (CRC). Nevertheless, most current screening programs suffer from low participation rates. A blood test may improve both the adherence to screening and the selection to colonoscopy. In this study, we conducted a serum-based discovery and validation of cfDNA methylation biomarkers for CRC screening in a multicentre cohort of 453 serum samples including healthy controls, benign pathologies, advanced adenomas (AA), and CRC. First, we performed an epigenome-wide methylation analysis with the MethylationEPIC array using a sample pooling approach, followed by a robust prioritization of candidate biomarkers for the detection of advanced neoplasia (AN: AA and CRC). Then, candidate biomarkers were validated by pyrosequencing in independent individual cfDNA samples. We report GALNT9, UPF3A, WARS, and LDB2 as new non-invasive biomarkers for the early detection of AN. The combination of GALNT9/UPF3A by logistic regression discriminated AN with 78.8% sensitivity and 100% specificity, outperforming the commonly used fecal immunochemical test and the methylated SEPT9 blood test. Overall, our results suggest that the combination methylated GALNT9/UPF3A has the potential to serve as a highly specific and sensitive blood-based test for screening and early detection of CRC.


2019 ◽  
pp. 1-22 ◽  
Author(s):  
Gilberto Lopes ◽  
Mariana C. Stern ◽  
Sarah Temin ◽  
Ala I. Sharara ◽  
Andres Cervantes ◽  
...  

PURPOSE To provide resource-stratified, evidence-based recommendations on the early detection of colorectal cancer in four tiers to clinicians, patients, and caregivers. METHODS American Society of Clinical Oncology convened a multidisciplinary, multinational panel of medical oncology, surgical oncology, surgery, gastroenterology, health technology assessment, cancer epidemiology, pathology, radiology, radiation oncology, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (Consensus Ratings Group) for two round(s) of formal ratings. RESULTS Existing sets of guidelines from eight guideline developers were identified and reviewed; adapted recommendations form the evidence base. These guidelines, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of 75% or more. CONCLUSION In nonmaximal settings, for people who are asymptomatic, are ages 50 to 75 years, have no family history of colorectal cancer, are at average risk, and are in settings with high incidences of colorectal cancer, the following screening options are recommended: guaiac fecal occult blood test and fecal immunochemical testing (basic), flexible sigmoidoscopy (add option in limited), and colonoscopy (add option in enhanced). Optimal reflex testing strategy for persons with positive screens is as follows: endoscopy; if not available, barium enema (basic or limited). Management of polyps in enhanced is as follows: colonoscopy, polypectomy; if not suitable, then surgical resection. For workup and diagnosis of people with symptoms, physical exam with digital rectal examination, double contrast barium enema (only in basic and limited); colonoscopy; flexible sigmoidoscopy with biopsy (if contraindication to latter) or computed tomography colonography if contraindications to two endoscopies (enhanced only).


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