scholarly journals Combining Serum DNA Methylation Biomarkers and Protein Tumor Markers Improved Clinical Sensitivity for Early Detection of Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Guoying Zhang ◽  
Fang He ◽  
Guodong Zhao ◽  
Zihui Huang ◽  
Xiang Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Markers ◽  
Clinical Performance ◽  
Screening Method ◽  
Blood Chemistry ◽  
Advanced Adenoma ◽  
Crc Screening ◽  
Control Subjects ◽  
Incidence And Mortality ◽  
Small Polyp

Background. Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide and in China. Early CRC screening is the best approach to reduce its incidence and mortality rates. The ColoDefense test, a multiplex qPCR assay simultaneously detecting both methylated SEPT9 and SDC2 genes, has demonstrated improved clinical performance on either methylation biomarker alone for CRC screening with both blood and stool samples. Method. Leftover blood chemistry test samples from 125 CRC, 35 advanced adenoma, and 35 small polyp patients and 92 healthy control subjects were examined by the ColoDefense test. Among these samples, the levels of three circulating tumor markers, CEA, AFP, and CA19-9, were also measured for 106 CRC, 28 advanced adenoma, and 20 small polyp patients and all control subjects. Results. Due to the smaller volume and extended storage in nonfrozen state, the ColoDefense test with these samples exhibited reduced performance for all stages of CRC and advanced adenomas. The performance of CEA, AFP, and CA19-9 and their various combinations was also evaluated for CRC screening to identify the tumor marker combinations with the best performance. When combined with the ColoDefense test, the identified combinations did improve the clinical performance. Conclusion. These results suggested a rational path towards developing a CRC screening method that takes advantage of leftover blood chemistry test samples. The successful development of such a method will undoubtedly help promote early CRC screening by increasing its accessibility for the general public.

scholarly journals KCNQ5 and C9orf50 Methylation in Stool DNA for Early Detection of Colorectal Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Yaping Cao ◽  
Guodong Zhao ◽  
Mufa Yuan ◽  
Xiaoyu Liu ◽  
Yong Ma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Performance ◽  
Advanced Adenoma ◽  
Early Colorectal Cancer ◽  
Crc Screening ◽  
Alternative Approach ◽  
Significant Difference ◽  
Stool Dna ◽  
Aberrant Dna Methylation ◽  
Screening And Prevention

BackgroundAberrant DNA methylation has emerged as a class of promising biomarkers for early colorectal cancer (CRC) detection, but the performance of methylated C9orf50 and methylated KCNQ5 in stool DNA has never been evaluated.MethodsMethylation specific quantitative PCR (qPCR) assays for methylated C9orf50 and methylated KCNQ5 were developed. The methylation levels of C9orf50 and KCNQ5 in 198 CRC patients, 20 advanced adenoma (AA) patients, 101 small polyp (SP) patients, and 141 no evidence of disease (NED) subjects were analyzed.ResultsThe methylation levels of both KCNQ5 and C9orf50 genes were significantly higher in CRC and AA groups than those in SP and NED groups, but showed no significant difference among different stages of CRC. The sensitivities of methylated KCNQ5 and methylated C9orf50 for CRC detection were 77.3% (95% CI: 70.7–82.8%) and 85.9% (95% CI: 80.0–90.2%) with specificities of 91.5% (95% CI: 85.3–95.3%) and 95.0% (95% CI: 89.7–97.8%), respectively. When C9orf50 and methylated KCNQ5 were combined, the clinical performance for CRC detection was similar to that of methylated C9orf50 alone.ConclusionsStool DNA based methylated C9orf50 test has the potential to become an alternative approach for CRC screening and prevention.

Opportunistic Colorectal Cancer Screening using Colonoscopy. Comparative Results between two Historical Cohorts in Bucharest, Romania

2015 ◽  
Vol 24 (2) ◽  
pp. 171-176 ◽  
Author(s):  
Elena Mirela Ionescu ◽  
Tudor Nicolaie ◽  
Serban Ion Gologan ◽  
Ana Mocanu ◽  
Cristina Ditescu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Screening Program ◽  
Advanced Adenoma ◽  
Detection Rates ◽  
Incidence And Mortality ◽  
Organized Screening Program ◽  
History Of ◽  
Comparative Results ◽  
Asymptomatic Individuals ◽  
Second Period

Background & Aims: Even though Romania has one of the highest incidence and mortality in colorectal cancer (CRC) in Europe, there is currently no organized screening program. We aimed to assess the results of our opportunistic CRC screening using colonoscopy.Methods: A single center retrospective study to include all opportunistic screening colonoscopies performed in two 18 month periods (2007-2008 and 2012-2013) was designed. All asymptomatic individuals without a personal or family history of adenoma or CRC and with complete colonoscopy performed in these two time periods were included.Results: We included 1,807 individuals, 882 in the first period, 925 in the second period. There were 389 individuals aged below 50, 1,351 between 50 and 75 and 67 older than 75 years. There were 956 women (52.9%), with a mean age of 58.5 (median 59, range 23-97). The detection rates were 12.6% for adenomas (6.1% for advanced adenoma) and 3.4% for adenocarcinoma. Adenoma incidence (4.9% in subjects under 50, 14.7% in those aged 50 to 75, and 16.4% in those older than 75, p<0.0001) and size (6.3mm in subjects younger than 50, 9.2mm in those 50 to 75 and 10.8mm in those older than 75, p=0.015) significantly increased with age. Adenoma incidence increased in the second period (14.8% vs. 10.3%, p=0.005), while adenoma size decreased in the second period (8.4mm vs. 10mm, p=0.006). There were no procedure related complications.Conclusions: The neoplasia detection rate was 16% (12.6% adenoma, 3.4% adenocarcinoma). Adenoma incidence and size increased with age in both cohorts. In the second screening period significantly more and smaller adenomas were detected.

scholarly journals The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ane Sørlie Kværner ◽  
Einar Birkeland ◽  
Cecilie Bucher-Johannessen ◽  
Elina Vinberg ◽  
Jan Inge Nordby ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Gut Microbiome ◽  
Precancerous Lesions ◽  
Colorectal Carcinogenesis ◽  
Screening Tools ◽  
Screening Methods ◽  
Crc Screening ◽  
Link Type ◽  
Incidence And Mortality

Abstract Background Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high. Trial registration ClinicalTrials.gov Identifier: NCT01538550.

Screening for colorectal cancer

2002 ◽  
Vol 39 (4) ◽  
pp. 351-365 ◽  
Author(s):  
Bryan J Starkey
Keyword(s):  
Colorectal Cancer ◽  
Screening Method ◽  
Point Mutations ◽  
Occult Blood ◽  
Crc Screening ◽  
Faecal Occult Blood ◽  
Faecal Occult ◽  
The Uk ◽  
Visualization Techniques ◽  
Stool Analysis

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.

scholarly journals The importance of colonoscopy bowel preparation for the detection of colorectal lesions and colorectal cancer prevention

2020 ◽  
Vol 08 (05) ◽  
pp. E673-E683 ◽  
Author(s):  
Prateek Sharma ◽  
Carol A. Burke ◽  
David A. Johnson ◽  
Brooks D. Cash
Keyword(s):  
Colorectal Cancer ◽  
Bowel Preparation ◽  
Clinical Importance ◽  
High Volume ◽  
High Quality ◽  
Crc Screening ◽  
Incidence And Mortality ◽  
Low Volume ◽  
Split Dosing ◽  
Bowel Preparations

Abstract Background and study aims Colonoscopy for colorectal cancer (CRC) screening has reduced CRC incidence and mortality and improved prognosis. Optimal bowel preparation and high-quality endoscopic technique facilitate early CRC detection.This review provides a narrative on the clinical importance of bowel preparation for colonoscopy and highlights available bowel preparations. Methods A PubMed search was conducted through June 2019 to identify studies evaluating clinical outcomes, efficacy, safety, and tolerability associated with bowel preparation for CRC screening-related colonoscopy. Results Selecting the optimal bowel preparation regimen is based on considerations of efficacy, safety, and tolerability, in conjunction with individual patient characteristics and preferences. Available bowel preparations include high-volume (4 L) and low-volume (2 L and 1 L), polyethylene glycol (PEG) solutions, sodium sulfate, sodium picosulfate/magnesium oxide plus anhydrous citric acid, sodium phosphate tablets, and the over-the-counter preparations magnesium citrate and PEG-3350. These preparations may be administered as a single dose on the same day or evening before, or as two doses administered the same day or evening before/morning of colonoscopy. Ingesting at least half the bowel preparation on the day of colonoscopy (split-dosing) is associated with higher adequate bowel preparation quality versus evening-before dosing (odds ratio [OR], 2.5; 95 % confidence interval [CI], 1.9−3.4). Conclusions High-quality bowel preparation is integral for optimal CRC screening/surveillance by colonoscopy. Over the last 30 years, patients and providers have gained more options for bowel preparation, including low-volume agents with enhanced tolerability and cleansing quality that are equivalent to 4 L preparations. Split-dosing is preferred for achieving a high-quality preparation.

scholarly journals Is Colorectal Cancer Screening Appropriate in Nigeria?

2019 ◽  
pp. 1-10
Author(s):  
Gregory C. Knapp ◽  
Olusegun I. Alatise ◽  
Olalekan O. Olasehinde ◽  
Ademola Adeyeye ◽  
Omobolaji O. Ayandipo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Parasitic Infection ◽  
Molecular Profile ◽  
Future Research ◽  
Middle Income ◽  
Crc Screening ◽  
Middle Income Countries ◽  
Incidence And Mortality ◽  
Prospective Trials ◽  
The Impact

PURPOSE The global burden of colorectal cancer (CRC) will continue to increase for the foreseeable future, largely driven by increasing incidence and mortality in low- and middle-income countries (LMICs) such as Nigeria. METHODS We used the Wilson-Jungner framework (1968) to review the literature relevant to CRC screening in Nigeria and propose areas for future research and investment. RESULTS Screening is effective when the condition sought is both important and treatable within the system under evaluation. The incidence of CRC is likely increasing, although the exact burden of disease in Nigeria remains poorly understood and access to definitive diagnosis and treatment has not been systematically quantified. In high-income countries (HICs), CRC screening builds on a well-known natural history. In Nigeria, a higher proportion of CRC seems to demonstrate microsatellite instability, which is dissimilar to the molecular profile in HICs. Prospective trials, tissue banking, and next-generation sequencing should be leveraged to better understand these potential differences and the implications for screening. Fecal immunochemical test for hemoglobin (FIT) is recommended for LMICs that are considering CRC screening. However, FIT has not been validated in Nigeria, and questions about the impact of high ambient temperature, endemic parasitic infection, and feasibility remain unanswered. Prospective trials are needed to validate the efficacy of stool-based screening, and these trials should consider concomitant ova and parasite testing. CONCLUSION Using the Wilson-Jungner framework, additional work is needed before organized CRC screening will be effective in Nigeria. These deficits can be addressed without missing the window to mitigate the increasing burden of CRC in the medium to long term.

scholarly journals Fecal Immunochemical Test as a Screening Method for Colorectal Cancer in University College Hospital Ibadan, Nigeria

2020 ◽  
pp. 525-531
Author(s):  
Elizabeth O. Labaeka ◽  
Achiaka E. Irabor ◽  
David O. Irabor
Keyword(s):  
Colorectal Cancer ◽  
Screening Method ◽  
Digital Rectal Examination ◽  
Fecal Immunochemical Test ◽  
Positive Finding ◽  
College Hospital ◽  
Crc Screening ◽  
University College ◽  
Immunochemical Test ◽  
Ibadan Nigeria

PURPOSE Colorectal cancer (CRC) is a disease of public health importance because of the increasing incidence of the disease and presentation in advanced stage of the disease in Western Africa. CRC is amenable to screening because of the long course of premalignant lesions before final development of the disease. Despite this, the practice of CRC screening is inadequate at the sites in this study. The fecal immunochemical test (FIT) is one of the recommended noninvasive methods for CRC screening. It has a sensitivity of 96%, specificity of 90%, and an overall accuracy of 95%. We aimed to determine the practicability of FIT for CRC screening in patients aged 40 to 75 years who attended primary care clinics in the University College Hospital, Ibadan, Nigeria. PATIENTS AND METHODS A total of 422 patients selected by systematic random sampling were recruited and offered free FIT screening. Participants with a positive finding had additional GI examination, including a digital rectal examination, proctoscopy, and colonoscopy, if no lesion was biopsied during proctoscopy. RESULTS The mean (± standard deviation) age of the respondents was 62 ± 9.61 years. The prevalence of a positive FIT in the study was 10.1%. The FIT was not completed by 3.8% of patients, and the rate of completion of additional evaluation after a positive FIT reduced as the investigations became invasive, with 36.8% and 71.1% noncompletion rates for proctoscopy and colonoscopy, respectively. CONCLUSION A FIT-based screening for age and risk-appropriate patients is practical in this environment, where the capacity and acceptability of colonoscopy are limited.

scholarly journals Analysis of A 6-Mirna Signature in Serum from Colorectal Cancer Screening Participants as Non-Invasive Biomarkers for Advanced Adenoma and Colorectal Cancer Detection

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1542 ◽  
Author(s):  
María Marcuello ◽  
Saray Duran-Sanchon ◽  
Lorena Moreno ◽  
Juan José Lozano ◽  
Luis Bujanda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Detection ◽  
Diagnostic Performance ◽  
Colorectal Neoplasia ◽  
Precancerous Lesion ◽  
Advanced Adenoma ◽  
Average Risk ◽  
Mirna Signature ◽  
Crc Screening ◽  
Non Invasive

Early detection of colorectal cancer (CRC) and its precancerous lesion, advanced adenomas (AA), is critical to improve CRC incidence and prognosis. Circulating microRNAs (miRNAs or miR) are promising non-invasive biomarkers for cancer detection. Our previous results showed that a plasma 6-miRNA signature (miR-15b-5p, miR-18a-5p, miR-29a-3p, miR-335-5p, miR-19a-3p and miR-19b-3p) could distinguish between CRC or AA and healthy individuals (controls). However, its diagnostic performance in serum is unknown. In this exploratory study we aim to evaluate the diagnostic performance of the 6-miRNA signature in serum samples in a cohort of individuals participating in Barcelona’s CRC Screening Programme. We prospectively collected serums from 264 faecal immunochemical test (FIT)-positive participants and total RNA was extracted. Finally, 213 individuals (CRC, 59, AA, 74, controls, 80) were included. MiRNA expression was quantified by real-time RT-qPCR and data analysis was performed by logistic regression. Faecal hemoglobin concentration (f(Hb)) from FIT of the same individuals was also considered. As previously described in plasma, serum from patients with AA or CRC presented significant differences in the 6-miRNA signature compared to controls. Moreover, when combined with f(Hb), the final signature showed high discriminative capacity to distinguish CRC from controls (area under the curve (AUC) = 0.88), and even AA (AUC = 0.81) that otherwise are poorly detected if we only consider f(Hb) (AUC = 0.64). Addition of the serum 6-miRNA signature to quantitative f(Hb) show high accuracy to detect patients with advanced colorectal neoplasia in average-risk individuals. A combination of these two non-invasive methods could be a good strategy to improve diagnostic performances of current CRC screening programmes.

An Electronic Questionnaire to Survey Colorectal Cancer Screening Status and Identify High-Risk Cohorts in Large Health Care Organizations

2020 ◽  
pp. 106286062093723
Author(s):  
Christopher T. Soriano ◽  
Thomas J. McGarrity ◽  
Junjia Zhu ◽  
Justin Loloi ◽  
Laurie P. Peiffer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Health Care ◽  
High Risk ◽  
Human Resources ◽  
Health Care Organizations ◽  
Response Rate ◽  
Patient Questionnaire ◽  
Screening Practices ◽  
Crc Screening ◽  
Incidence And Mortality

Though improved screening practices have reduced the incidence and mortality of colorectal cancer (CRC), screening rates continue to be suboptimal. This is especially true of high-risk individuals, who are difficult for clinicians to identify during a typical health care encounter. The authors developed an electronic patient questionnaire that determined an individual’s CRC screening status and identified high-risk individuals. The questionnaire was administered to employees through the Department of Human Resources. The response rate was 44.7%; 81.2% of respondents aged ≥50 years were up-to-date on CRC screening; 878 high-risk individuals were identified, 77.7% of whom were up-to-date on CRC screening. However, among high-risk individuals aged 40 to 49 years, only 45.8% reported up-to-date CRC screening. The questionnaire was effective in measuring CRC screening rates and identifying high-risk individuals. Dissemination by the Department of Human Resources was novel, effective, and was not dependent on a health care encounter to assess screening or high-risk status.

The impact of colorectal cancer screening on incidence and stage IV disease in the Netherlands.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3531-3531
Author(s):  
Myrtle F Krul ◽  
Marloes AG Elferink ◽  
Niels FM Kok ◽  
Evelien Dekker ◽  
Iris Lansdorp-Vogelaar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
The Netherlands ◽  
Local Treatment ◽  
Stage Iv ◽  
Stage I ◽  
Crc Screening ◽  
Stage Distribution ◽  
Incidence And Mortality ◽  
Stage Iv Disease ◽  
The Impact

3531 Background: Population-based screening for colorectal cancer (CRC) aims to decrease incidence and mortality due to precancerous polyp removal, early detection and early treatment of CRC. In the Netherlands, phased introduction of a biennial fecal immunochemical hemoglobin test started in 2014 for individuals aged 55-75. This evaluation of the national data focuses on the initial effect of CRC screening on incidence and stage distribution and the impact on stage IV disease. Methods: All CRC patients diagnosed in the Netherlands between 2009 and 2018 were selected from the Netherlands Cancer Registry (NCR). Patients were linked to the Dutch national pathology registry (PALGA) to identify screen-detected tumors. Results: The NCR identified 137,717 CRC patients between 2009 and 2018. The incidence within screening age (55-75 yr) of all CRC stages showed an initial peak after introduction of screening in 2014, followed by a continuous decrease for all stages. CRC incidence outside the screening age did not show these explicit changes between 2009 and 2018. In 2018, the incidence of stage IV CRC within screening age was lower than the level at the start of the screening program. Stage distribution within screening age shifted towards earlier stages in the screening period (2014-2018) compared to the period before screening (2009-2012) (stage I: 31% vs. 18%, stage II: 22% vs. 26%, stage III: 29% vs. 31%, Stage IV: 18% vs. 25%, respectively). In the period 2014-2018 and within screening age, the ratio of screen-detected and symptom-detected tumors was highest in stage I (47%:53%) and lowest in stage IV (9%:91%). Screen-detected compared to symptom-detected stage IV patients diagnosed in the period 2014-2018 and within screening age had more frequently single organ metastases (74.5% vs 57.4%, p < 0.001), higher resection rate of the primary tumor (57.5% vs. 41.3%; p < 0.001) and higher local treatment rate of metastases (40.0% vs. 23.4% p < 0.001). The median overall survival of screen-detected stage IV patients was significantly longer than that of symptom-detected stage IV patients (31.0 months (95% CI: 27.7 – 34.3) vs. 15.0 months (95% CI: 14.5 – 15.5), p < 0.001). Conclusions: The initial results of the introduction of CRC screening in the Netherlands showed a favorable trend on CRC incidence and stage distribution. Screen-detected patients with stage IV disease had less extensive disease, resulting in better treatment options and improved survival.

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