The Importance of Molecular Diagnostics and Screening Programs in Monitoring
and Evaluation of Colorectal Cancer in the Republic of North Macedonia

Colorectal cancer (CRC) is one of the most common malignant diseases (12 % of the total) that occurs with an incidence of 15 – 30 new cases per 100,000 population per year in European Union countries. The risk of this disease during life depends on many factors such as age, diet, physical activity, personal and family predisposition. Several preventive measures can reduce the number of colorectal cancer patients. First of all, the regular screening which allows the detection of precancerous polyps or cancer in the early stage and their successful surgical removal. The purpose of this paper is to highlight the importance of screening programs as a preventive measure for the early detection of colorectal cancer and to reduce the morbidity and mortality of this disease. The strategy for improving the early detection of colorectal cancer also implies availability of useful information about the importance of screening programs for everyone as well as educating health care staff about the program itself. Number of newly registered colorectal cancer cases in 2009 in the Republic North Macedonia stands at 547 with a rate of 26.7 compared to 2018 with 839 newly registered cases with a rate of 40.4 which clearly indicates an increasing trend of colorectal cancer. Multidisciplinary approach to early detection of colorectal cancer, continuity of Program funding and quality of services will lead to reduction of morbidity and mortality of this type of cancer.

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

BMC Gastroenterology ◽

10.1186/s12876-021-01759-9 ◽

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.

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Non-invasive colorectal cancer screening

University of Western Ontario Medical Journal ◽

10.5206/uwomj.v85i2.2231 ◽

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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Towards Novel Non-Invasive Colorectal Cancer Screening Methods: A Comprehensive Review

10.20944/preprints202103.0448.v1 ◽

2021 ◽

Author(s):

Allegra Ferrari ◽

Isabelle Neefs ◽

Sarah Hoeck ◽

Marc Peeters ◽

Guido Van Hal

Keyword(s):

Colorectal Cancer ◽

Early Stage ◽

Screening Tests ◽

Screening Methods ◽

Exhaled Breath ◽

Sample Collection ◽

Screening Programs ◽

Crc Screening ◽

Low Sensitivity ◽

Standard Colonoscopy

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.

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A VIEW ON THE PROBLEM OF INADEQUATE SCREENING OF COLORECTAL CANCER IN UKRAINE

Likarska sprava ◽

10.31640/jvd.3.2019(1) ◽

2019 ◽

pp. 3-5

Author(s):

Nelya Melnitchouk ◽

Galyna Shabat

Keyword(s):

Colorectal Cancer ◽

Clinical Symptoms ◽

Screening Program ◽

Early Stage ◽

Cancer Death ◽

Common Cause ◽

Screening Programs ◽

Incidence And Mortality ◽

National Organizations

The incidence of colorectal cancer (CRC) is increasing worldwide and it is the second most common cause of cancer death. There is a lot of investigations and improvement to rise quality of early diagnosis, successful treatment and effective preventions of colorectal cancer. Nowadays available few guidelines of international and national organizations what support effectiveness of screening programs. Colorectal cancer screening is effective way to decrease incidence and mortality with strong evidence confirmed by a lot of investigations of different scientific groups. Currently, Ukraine doesn’t have an established colorectal cancer program, what need to be changed as soon as possible. A lot of patients in Ukraine wait at home till the beginning of clinical symptoms, what often is the representation of later stage of diseases; and of course treatment of patients with later stage of diseases need more costs for treatment and show worst results of morbidity and mortality rate compare with patients treated at the early stage of diseases. We created a simulation Markov model and demonstrated that the implementation of the national screening program for colorectal cancer in Ukraine will be cost saving and will decrease the mortality from colorectal cancer significantly.

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Lifestyle Modification

American Journal of Lifestyle Medicine ◽

10.1177/1559827612436943 ◽

2012 ◽

Vol 6 (3) ◽

pp. 216-218

Author(s):

Craig A. Johnston ◽

Jennette P. Moreno

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Early Detection Of Cancer ◽

Lifestyle Modification ◽

Primary Treatment ◽

Morbidity And Mortality ◽

Lifestyle Interventions ◽

Lifestyle Behaviors ◽

Lifestyle Practices ◽

Reduced Risk

Early detection of cancer through screening is an important step in decreasing both morbidity and mortality. Likewise, specific modifiable lifestyle behaviors are associated with reduced risk of colorectal cancer. Lifestyle practices have also been shown to maximize health after the primary treatment of cancer. Both these roles for lifestyle interventions are discussed.

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Use of Biomarkers and Imaging for Early Detection of Pancreatic Cancer

Cancers ◽

10.3390/cancers12071965 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1965 ◽

Cited By ~ 2

Author(s):

Shingo Kato ◽

Kazufumi Honda

Keyword(s):

Pancreatic Cancer ◽

General Population ◽

Early Detection ◽

Early Stage ◽

Precancerous Lesions ◽

Imaging Techniques ◽

Circulating Tumor Dna ◽

Proton Density ◽

Screening Programs ◽

Pancreatic Steatosis

Pancreatic cancer remains one of the deadliest cancers worldwide, and it is typically diagnosed late, with a poor prognosis. Early detection is the most important underlying factor for improving the prognosis of pancreatic cancer patients. One of the most effective strategies for detecting cancers at an early stage is screening of the general population. However, because of the low incidence of pancreatic cancer in the general population, the stratification of subjects who need to undergo further examinations by invasive and expensive modalities is important. Therefore, minimally invasive modalities involving biomarkers and imaging techniques that would facilitate the early detection of pancreatic cancer are highly needed. Multiple types of new blood biomarkers have recently been developed, including unique post-translational modifications of circulating proteins, circulating exosomes, microRNAs, and circulating tumor DNA. We previously reported that circulating apolipoprotein A2 undergoes unique processing in the bloodstream of patients with pancreatic cancer and its precancerous lesions. Additionally, we recently demonstrated a new method for measuring pancreatic proton density in the fat fraction using a fat–water magnetic resonance imaging technique that reflects pancreatic steatosis. In this review, we describe recent developments in potential biomarkers and imaging modalities for the early detection and risk stratification of pancreatic cancer, and we discuss current strategies for implementing screening programs for pancreatic cancer.

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

10.1101/2021.11.11.21266182 ◽

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.

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Usefulness of Screening for Hypertension

PEDIATRICS ◽

10.1542/peds.73.6.883d ◽

1984 ◽

Vol 73 (6) ◽

pp. 883-884

Author(s):

DAVID E. FIXLER

Keyword(s):

Early Detection ◽

Mass Screening ◽

Screening Program ◽

Morbidity And Mortality ◽

Screening Procedure ◽

High Yield ◽

Health Consequences ◽

Screening Programs ◽

Appropriate Treatment ◽

Number Of Patients

In Reply.— Grossman has expressed the opinion that among the criteria for any screening procedure is that the disease being screened for is either prevalent or has severe health consequences. Although these are notable criteria, they in no means represent indications for initiating mass screening programs. Justification for a screening program is based on its having a high yield, that is, that early detection in a significant number of patients will lead to appropriate treatment and a significant decrease in morbidity and mortality.

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Identification of microbial markers across populations in early detection of colorectal cancer

Nature Communications ◽

10.1038/s41467-021-23265-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yuanqi Wu ◽

Na Jiao ◽

Ruixin Zhu ◽

Yida Zhang ◽

Dingfeng Wu ◽

...

Keyword(s):

Colorectal Cancer ◽

Functional Analysis ◽

Random Forest ◽

Early Detection ◽

Early Diagnosis ◽

Gut Microbiota ◽

Early Stage ◽

Control Area ◽

Integrated Analysis ◽

Quantitative Real Time Pcr

AbstractAssociations between gut microbiota and colorectal cancer (CRC) have been widely investigated. However, the replicable markers for early-stage adenoma diagnosis across multiple populations remain elusive. Here, we perform an integrated analysis on 1056 public fecal samples, to identify adenoma-associated microbial markers for early detection of CRC. After adjusting for potential confounders, Random Forest classifiers are constructed with 11 markers to discriminate adenoma from control (area under the ROC curve (AUC) = 0.80), and 26 markers to discriminate adenoma from CRC (AUC = 0.89), respectively. Moreover, we validate the classifiers in two independent cohorts achieving AUCs of 0.78 and 0.84, respectively. Functional analysis reveals that the altered microbiome is characterized with increased ADP-l-glycero-beta-d-manno-heptose biosynthesis in adenoma and elevated menaquinone-10 biosynthesis in CRC. These findings are validated in a newly-collected cohort of 43 samples using quantitative real-time PCR. This work proves the validity of adenoma-specific markers across multi-populations, which would contribute to the early diagnosis and treatment of CRC.

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MAP17 Expression in Colorectal Cancer Is a Prognostic Factor for Disease Recurrence and Dismal Prognosis Already in Early Stage Disease

Oncology ◽

10.1159/000515596 ◽

2021 ◽

pp. 1-11

Author(s):

Athanasios Tampakis ◽

Ekaterini Christina Tampaki ◽

Afroditi Nonni ◽

Michael Kontos ◽

Gerasimos Tsourouflis ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Cancer Cells ◽

Early Stage ◽

Progression Free Survival ◽

Disease Recurrence ◽

Morbidity And Mortality ◽

Early Stage Disease ◽

Free Survival ◽

Stage Disease

Background: Disease recurrence in colorectal cancer constitutes a major cause of significant cancer-associated morbidity and mortality. MAP17 is a small protein, and its overexpression in malignant tumors has been correlated with aggressive tumor phenotypes. The aim of the present study was to investigate the expression patterns of MAP17 in colorectal cancer specimens and to assess its clinical significance. Patients and Methods: Surgical specimens of 111 patients with primary resectable colorectal cancer constituted the study population. Expression of MAP17 was assessed by immunohistochemistry, and the results were correlated with clinical and survival data. Results: MAP17 was expressed in cancer cells and endothelial cells of tumor blood vessels. Expression of MAP17 more than 10% was correlated with advanced disease stage (p < 0.001), higher T classification (p = 0.007), the presence of lymph node metastasis (p < 0.001), vascular (p = 0.013) and perineural invasion (p = 0.012). Patients exhibiting MAP17 expression of more than 30% in cancer cells compared to those expressing MAP17 less than 10% demonstrated a significantly worse 3-year progression-free survival (35.2 vs. 91%, p < 0.001) and 5-year overall survival (40.8 vs. 91%, p < 0.001). Cox regression analysis confirmed MAP17 expression of more than 30% as a prognostic marker of progression free survival (HR 0.136, 95% CI = 0.056–0.329, p < 0.001) and overall survival (HR 0.144 [95% CI) = 0.049–0.419, p < 0.001) independent of other clinicopathological characteristics. Statistically significantly worse 3-year progression-free survival and 5-year overall survival was demonstrated in the subgroup analysis of patients with early stage cancer only and high expression of MAP17. Conclusions: High MAP17 expression in patients with colorectal cancer is a significant risk factor for cancer-associated morbidity and mortality already in early stage disease.

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