scholarly journals Highly-specific early detection of colorectal cancer by novel non-invasive serum methylation biomarkers

2021 ◽  
Author(s):  
Maria Gallardo-Gomez ◽  
Mar Rodriguez-Girondo ◽  
Nuria Planell ◽  
Sebastian Moran ◽  
Luis Bujanda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Blood Test ◽  
Serum Samples ◽  
Screening Programs ◽  
Non Invasive ◽  
Incidence And Mortality ◽  
Sample Pooling ◽  
Immunochemical Test ◽  
Advanced Adenomas

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.

scholarly journals New fecal bacterial signature for colorectal cancer screening reduces the fecal immunochemical test false-positive rate in a screening population

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243158
Author(s):  
Marta Malagón ◽  
Sara Ramió-Pujol ◽  
Marta Serrano ◽  
Joan Amoedo ◽  
Lia Oliver ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
False Positive ◽  
False Positive Rate ◽  
Fecal Immunochemical Test ◽  
Noninvasive Test ◽  
Screening Programs ◽  
Crc Screening ◽  
Positive Rate ◽  
Immunochemical Test ◽  
Advanced Adenomas

Guidelines recommend routine screening for colorectal cancer (CRC) in asymptomatic adults starting at age 50. The most extensively used noninvasive test for CRC screening is the fecal immunochemical test (FIT), which has an overall sensitivity for CRC of approximately 61.0%-91.0%, which drops to 27.0%-67.0% for advanced adenomas. These figures contain a high false-positive rate and a low positive predictive value. This work aimed to develop a new, noninvasive CRC screening tool based on fecal bacterial markers capable of decreasing FIT false-positive rates in a FIT-positive population. We defined a fecal bacterial signature (RAID-CRC Screen) in a proof-of-concept with 172 FIT-positive individuals and validated the obtained results on an external cohort of 327 FIT-positive subjects. All study participants had joined the national CRC screening program. In the clinical validation of RAID-CRC Screen, a sensitivity of 83.9% and a specificity of 16.3% were obtained for the detection of advanced neoplasm lesions (advanced adenomas and/or CRC). FIT 20 μg/g produced 184 false-positive results. Using RAID-CRC Screen, this value was reduced to 154, thus reducing the false-positive rate by 16.3%. The RAID-CRC Screen test could be implemented in CRC screening programs to allow a significant reduction in the number of colonoscopies performed unnecessarily for FIT-positive participants of CRC screening programs.

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
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Blood Test ◽  
Clinical Status ◽  
Screening Method ◽  
Fecal Occult Blood ◽  
Average Risk ◽  
Serum Samples ◽  
Noninvasive Test ◽  
Epigenetic Biomarkers

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.

scholarly journals Are Volatile Organic Compounds Accurate Markers in the Assessment of Colorectal Cancer and Inflammatory Bowel Diseases? A Review

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2361
Author(s):  
Filippo Vernia ◽  
Marco Valvano ◽  
Stefano Fabiani ◽  
Gianpiero Stefanelli ◽  
Salvatore Longo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Volatile Organic Compounds ◽  
Organic Compounds ◽  
Inflammatory Bowel Diseases ◽  
Screening Programs ◽  
Inflammatory Status ◽  
Incidence And Mortality ◽  
Volatile Organic ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the Western world. Early detection decreases incidence and mortality. Screening programs based on fecal occult blood testing help identify patients requiring endoscopic examination, but accuracy is far from optimal. Among the alternative strategies, volatile organic compounds (VOCs) represent novel potentially useful biomarkers of colorectal cancer. They also represent a promising tool for the screening of both intestinal inflammation and related CRC. The review is focused on the diagnostic potential of VOCs in sporadic CRC and in inflammatory bowel diseases (IBD), which increase the risk of CRC, analyzing future clinical applications. Despite limitations related to inadequate strength of evidence, differing analytical platforms identify different VOCs, and this unconventional approach for diagnosing colorectal cancer is promising. Some VOC profiles, besides identifying inflammation, seem disease-specific in inflammatory bowel diseases. Thus, breath, urine, and fecal VOCs provide a new and promising clinical approach to differential diagnosis, evaluation of the inflammatory status, and possibly the assessment of treatment efficacy in IBD. Conversely, specific VOC patterns correlating inflammatory bowel disease and cancer risk are still lacking, and studies focused on this issue are strongly encouraged. No prospective studies have assessed the risk of CRC development by using VOCs in samples collected before the onset of disease, both in the general population and in patients with IBD.

scholarly journals Colorectal cancer screening using a stool DNA-based SDC2 methylation test: a multicenter, prospective trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chang Woo Kim ◽  
Hyunjin Kim ◽  
Hyoung Rae Kim ◽  
Bong-Hyeon Kye ◽  
Hyung Jin Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Early Detection ◽  
Prospective Trial ◽  
Screening Colonoscopy ◽  
Quantitative Detection ◽  
Screening Programs ◽  
Crc Screening ◽  
Stool Dna ◽  
Dna 2

Abstract Background Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. Methods All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central laboratory for analysis. Stool DNA will be isolated using a GT Stool DNA Extraction kit, according to the manufacturer’s protocol. Before performing the methylation test, stool DNA (2 µg per reaction) will be treated with bisulfite, according to manufacturer’s instructions. SDC2 and COL2A1 control reactions will be performed in a single tube. The SDC2 methylation test will be performed using an AB 7500 Fast Real-time PCR system. CT values will be calculated using the 7500 software accompanying the instrument. Results from the EarlyTect™-Colon Cancer test will be compared against those obtained from colonoscopy and any corresponding diagnostic histopathology from clinically significant biopsied or subsequently excised lesions. Based on these results, participants will be divided into three groups: CRC, polyp, and negative. The following clinical data will be recorded for the participants: sex, age, colonoscopy results, and clinical stage (for CRC cases). Discussion This trial investigates the clinical performance of a device that allows quantitative detection of a single DNA marker, SDC2 methylation, in human stool DNA in asymptomatic populations. The results of this trial are expected to be beneficial for CRC screening and may help make colonoscopy a selective procedure used only in populations with a high risk of CRC. Trial registration: This trial (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020 and is available at https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1.

scholarly journals Selection of patients for large mailed fecal immunochemical test colorectal cancer screening outreach programs: A systematic review

2021 ◽  
pp. 096914132199748
Author(s):  
Andrew Wang ◽  
Briton Lee ◽  
Shreya Patel ◽  
Evans Whitaker ◽  
Rachel B Issaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Health Care ◽  
Cancer Screening ◽  
Patient Selection ◽  
Implementation Strategies ◽  
Screening Programs ◽  
Crc Screening ◽  
Key Informant ◽  
Immunochemical Test

Objective Digital health care offers an opportunity to scale and personalize cancer screening programs, such as mailed outreach for colorectal cancer (CRC) screening. However, studies that describe the patient selection strategy and process for CRC screening are limited. Our objective was to evaluate implementation strategies for selecting patients for CRC screening programs in large health care systems. Methods We conducted a systematic review of 30 studies along with key informant surveys and interviews to describe programmatic implementation strategies for selecting patients for CRC screening. PubMed and Embase were searched since inception through December 2018, and hand searches were performed of the retrieved reference lists but none were incorporated ( n = 0). No language exclusions were applied. Results Common criteria for outreach exclusion included: being up-to-date with routine CRC screening ( n = 22), comorbidities ( n = 20), and personal history ( n = 22) or family history of cancer ( n = 9). Key informant surveys and interviews were performed ( n = 28) to understand data sources and practices for patient outreach selection, and found that 13 studies leveraged electronic medical care records, 10 studies leveraged a population registry (national, municipal, community, health), 4 studies required patient opt-in, and 1 study required primary care provider referral. Broad ranges in fecal immunochemical test completion were observed in community clinic ( n = 8, 31.0–59.6%), integrated health system ( n = 5, 21.2–82.7%), and national regional CRC screening programs ( n = 17, 23.0–64.7%). Six studies used technical codes, and four studies required patient self-reporting from a questionnaire to participate. Conclusion This systematic review provides health systems with the diverse outreach practices and technical tools to support efforts to automate patient selection for CRC screening outreach.

scholarly journals Immunochemical Fecal Occult Blood Test for Detection of Advanced Colonic Adenomas and Colorectal Cancer: Comparison with Colonoscopy Results

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Bianca Rosa Viana Freitas ◽  
Cristiane Kibune Nagasako ◽  
Celia Regina Pavan ◽  
Sônia Letícia Silva Lorena ◽  
Fabio Guerrazzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sensitivity And Specificity ◽  
Occult Blood ◽  
Fecal Occult Blood ◽  
Screening Programs ◽  
Fecal Occult ◽  
Colonic Adenomas ◽  
Lack Of Information ◽  
Risk Patients ◽  
Advanced Adenomas

Background. Fecal immunochemical tests (FITs) have been used for colorectal cancer (CRC) screening in several countries. There is lack of information concerning diagnostic performances of this method in Brazil.Methods. Patients scheduled for elective colonoscopy provided one stool sample one week before colonoscopy. The accuracy of a qualitative FIT for detection of CRC and advanced adenomas was determined.Results. Overall 302 patients completed the study. Among them, 53.5% were high risk patients referred for screening or surveillance. Nine (3%) CRCs and 11 (3.6%) advanced adenomas were detected by colonoscopy. Sensitivity and specificity for CRC were, respectively, 88.9% and 87.6%. For advanced adenomas, sensitivity was 63.6% and specificity 87.6%.Conclusion. Our results showed good sensitivity and specificity of the FIT for detecting advanced neoplasias. This method may be a valuable tool for future screening programs in Brazil.

scholarly journals Colorectal Cancer in Young and Older Adults in Uruguay: Changes in Recent Incidence and Mortality Trends

2021 ◽  
Vol 18 (15) ◽  
pp. 8232
Author(s):  
Carina Musetti ◽  
Mariela Garau ◽  
Rafael Alonso ◽  
Marion Piñeros ◽  
Isabelle Soerjomataram ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Older Adults ◽  
Cancer Incidence ◽  
Age Groups ◽  
Incidence Rates ◽  
Mortality Trends ◽  
Screening Programs ◽  
Lifestyle Risk Factors ◽  
Incidence And Mortality ◽  
Colorectal Cancer Incidence

Uruguay has the highest colorectal cancer incidence rates in Latin America. Previous studies reported a stable incidence and a slight increase in mortality among males. We aimed to assess colorectal cancer incidence (2002–2017) and mortality trends (1990–2017) by age groups and sex, using data from the National Cancer Registry. Annual percent changes (APCs) were estimated using joinpoint regression models. We included 27,561 colorectal cancer cases and 25,403 deaths. We found an increasing incidence among both males and females aged 40–49, with annual increases of 3.1% (95%CI: 1.21–5.03) and 2.1% (95%CI: 0.49–3.66), respectively, and an increasein the rate in older males (70+) of 0.60% (95%CI: 0.02–1.20) per year between 2002 and 2017. Mortality remained stable among those younger than 50, whereas it decreased for older females aged 50–69 and 70+ (APC: −0.61% (−1.07–0.14) and −0.68% (−1.02–0.34), respectively), and increased for the oldest males (70+; APC: 0.74 (0.47–1.01)). In conclusion, we found rising colorectal cancer incidence accompanied by stable mortality in young adults. Sex disparities were also found among the older adults, with a more favorable pattern for females. Exposures to dietary and lifestyle risk factors, and inequalities in access to and awareness of screening programs, are probably among the main underlying causes and deserve further investigation.

Persistent Barriers to Colorectal Cancer Screening Completion Amid Centralized Outreach: A Mixed Methods Study

2021 ◽  
pp. 089011712110644
Author(s):  
Jocelyn V. Wainwright ◽  
Shivan J. Mehta ◽  
Alicia Clifton ◽  
Claire Bocage ◽  
Shannon N. Ogden ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Comparative Method ◽  
Pragmatic Trial ◽  
Behavioral Model ◽  
Structural Barriers ◽  
Crc Screening ◽  
Non Invasive ◽  
Interview Guide ◽  
Timely Completion ◽  
Immunochemical Test

Purpose To understand patient experiences and persistent barriers to colorectal cancer (CRC) screening amid centralized outreach at urban family medicine practices. Approach Following a pragmatic trial assessing mailed fecal immunochemical test (FIT) outreach, we invited a subset of participants to complete a semi-structured qualitative interview and structured questionnaire. Setting Single urban academic healthcare system. Participants Sixty patients who were eligible and overdue for CRC screening at the time of trial enrollment. Method Using Andersen’s Behavioral Model, we developed an interview guide to systematically assess factors shaping screening decisions and FIT uptake. Close-ended responses were analyzed using descriptive statistics. Qualitative data were analyzed using the constant comparative method. Results Most participants (82%) self-reported that they had ever completed any modality of CRC screening, and nearly half (43%) completed the mailed FIT during the trial. Most patients (60%) preferred FIT to colonoscopy due to its private, convenient, and non-invasive nature; however, persistent barriers related to screening beliefs including fear of test results and cancer treatment still prevented some patients from completing any form of CRC screening. Conclusions Mailed FIT can overcome many structural barriers to CRC screening, yet clear communication and follow-up amid centralized outreach are essential. For some patients, tailored outreach or navigation to address screening-related fears or other screening beliefs may be needed to ensure timely completion of CRC screening.

scholarly journals Non-invasive colorectal cancer screening

2016 ◽  
Vol 85 (2) ◽  
pp. 29-31
Author(s):  
Melissa Holdren ◽  
Brittany Deller ◽  
Kevin Braden
Keyword(s):  
Colorectal Cancer ◽  
Developmental Process ◽  
Population Based ◽  
Adenomatous Polyps ◽  
Morbidity And Mortality ◽  
Screening Tests ◽  
Average Risk ◽  
Screening Programs ◽  
Asymptomatic Patients ◽  
Advanced Adenomas

Colorectal cancer (CRC) is a major cause of morbidity and mortality throughout the world and is the second most common cause of Canadian cancer-related deaths in men and the third most common in women. Most CRC appears to arise from the gradual development and advancement of colonic adenomatous polyps to cancerous tissue. This developmental process of CRC is the rationale for screening programs which aim to reduce CRC-related morbidity and mortality by early detection and removal of adenomatous polyps, specifically advanced adenomas. Although both the gFOBT and FIT function to detect occult bleeding in asymptomatic patients at average risk for CRC development, the mechanisms of these screening tests are distinct. gFOBT works by detecting the peroxidase activity of heme whereas FIT selectively detects human hemoglobin. The sensitivity in detecting CRC is higher for the FIT, with sensitivity of 0.79 compared to gFOBT with sensitivity of 0.36, they have similar specificities of 0.94 and 0.96, respectively. Currently, both the gFOBT and FIT are strongly recommended across Canada, with all provinces using the FIT, apart from Ontario and Manitoba which currently use the gFOBT to screen asymptomatic patients for CRC. A newer test, the sDNA test, identifies mutations in DNA that are shed by both adenomatous polyps and CRC cells. The sDNA test is more sensitive (0.92 95% CI 0.83-0.98) than both the gFOBT and FIT, however, is less specific and more expensive. Further data surrounding the sDNA test will be required prior to its implementation and recommendation for population based CRC screening in Canada. 

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