Predictors of circulating tumor-derived methylated BCAT1 and IKZF1 DNA in colorectal cancer patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 567-567
Author(s):  
Erin L Symonds ◽  
Susanne Kartin Pedersen ◽  
David Murray ◽  
Rohan Baker ◽  
Graeme P Young

567 Background: Blood tests detecting circulating tumor-derived DNA (ctDNA) are being developed for colorectal cancer (CRC) screening and monitoring. However, the underlying tumor biology resulting in circulating DNA is not well understood. This study aimed to elucidate tumor features associated with methylated BCAT1 and IKZF1 DNA in blood as well as patient demographics that predict biomarker appearance. Methods: 129 people with invasive CRC had blood collected prior to surgery. Patient sociodemographic factors were recorded. Extracted circulating cell-free DNA was assayed for methylated BCAT1 and IKZF1. Patient factors and tumor features including location, size, depth of invasion (T stage), degree of differentiation, vascularity, lymphatic and perineurial invasion, lymph node involvement and presence of metastasis were compared with blood test results using multivariate logistic regression analysis. Results: The distribution of CRC stages I to IV were 34, 43, 41 and 11, respectively and 72 (56%) were blood positive for methylated BCAT1/IKZF1. Positivity was associated with distally located tumors and a higher T stage (Table). Gender, age, BMI, race, smoking and medications were not associated with blood positivity rates, but increased alcohol intake ( > 7 drinks/week, n = 31) was associated (OR 5.7, 95% CI 1.1-28.7, p = 0.036). Conclusions: The strongest predictor for appearance of ctDNA was invasion depth of the tumor. Demographic features did not influence the positivity rate of the BCAT1/ IKZF1 CRC blood test, strengthening the validity of this blood test for CRC screening and monitoring in the general population. [Table: see text]

Healthcare ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 569
Author(s):  
Benjamin E. Ansa ◽  
Nicollette Lewis ◽  
Zachary Hoffman ◽  
Biplab Datta ◽  
J. Aaron Johnson

Colorectal cancer (CRC) is the third most prevalent cancer and the second most common cause of cancer-related deaths in the United States (USA). Early screening has been demonstrated to improve clinical outcomes for CRC. Assessing patterns in CRC screening utilization is important for guiding policy and implementing programs for CRC prevention and control. This study examines the trends and sociodemographic factors associated with blood stool test utilization (BSTU) for CRC screening in Georgia, USA. The Behavioral Risk Factor Surveillance System (BRFSS) data were analyzed for Average Annual Percent Change (AAPC) in BSTU between 1997 and 2014 among adults aged 50+ who have had a blood stool test within the past two years, and logistic regression analysis of the 2016 data was performed to identify the associated sociodemographic factors. In Georgia, an overall decrease was observed in BSTU, from 27.8% in 1997 to 16.1% in 2014 (AAPC = −2.6, p = 0.023). The decrease in BSTU was less pronounced in Georgia than nationally (from 26.1% in 1997 to 12.8% in 2014 (AAPC = −4.5, p < 0.001)). BSTU was significantly associated with black race/ethnicity (Black vs. White (aOR = 1.43, p = 0.015)), older age (≥70 vs. 50–59 (aOR = 1.62, p = 0.006)), having insurance coverage (no vs. yes (aOR = 0.37 p = 0.005)), and lower income (≥USD 50,000 vs. <USD 25,000 (aOR = 0.70 p = 0.050)). These findings reveal a decrease over time in BSTU in Georgia, with existing differences between sociodemographic groups. Understanding these patterns helps in directing tailored programs for promoting CRC screening, especially among disadvantaged populations.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Asma Althobaiti ◽  
Hoda Jradi

Abstract Background Colorectal cancer (CRC) is a major health problem. It is the third most diagnosed common tumour and the fourth leading cause of cancer-related deaths worldwide. Early screening has been shown to decrease the incidence of CRC cancer and decrease mortality. In Saudi Arabia (SA), there is no national policy for CRC screening despite the growing incidence of the disease. This study investigated the knowledge of risk factors for CRC, recommendations for screening, and attitudes and barriers towards screening among medical students. Methods Data was collected using a self-administered valid and reliable questionnaire consisting of demographic characteristics, knowledge, attitude, and barriers measurements completed by 581 medical students from two Saudi schools. Frequencies and mean scores of knowledge and attitude were determined. The likelihood of students having adequate knowledge of CRC risk factors and screening modalities was estimated using multivariate logistic regression analysis. Results Knowledge of the risk factors for CRC and screening modalities, and attitude towards screening were poor in 52.47 and 57.83% of the surveyed medical students; respectively. Higher level of medical education (OR = 3.23; 95% CI: 2.01–5.18) and a positive attitude towards CRC screening (OR = 2.74; 95% CI: 1.86–4.03) were independent predictors of higher knowledge levels. Lack of awareness about CRC and screening modalities among patients, and shortage of specialized healthcare providers were barriers independently associated with low knowledge levels. Conclusions Saudi medical students have limited knowledge of CRC risk factors of and a poor attitude towards CRC screening. These results contribute to our understanding of missed teaching opportunities in Saudi medical schools and suggest intervening at the medical school, clinical practice, and population levels to increase CRC screening practices.


2019 ◽  
Author(s):  
Asma Althobaiti ◽  
Hoda Jr

Abstract Background Colorectal cancer (CRC) is a major health problem. It is the third most diagnosed common tumour and the fourth leading cause of cancer-related deaths worldwide. Early screening has been shown to decrease the incidence of CRC cancer and decrease mortality. In Saudi Arabia (SA), there is no national policy for CRC screening despite the growing incidence of the disease.This study investigated the knowledge of risk factors for CRC, recommendations for screening, and attitudes and barriers towards screening among medical students. Methods Data was collected using a self-administered valid and reliable questionnaire consisting of demographic characteristics, knowledge, attitude, and barriers measurements completed by 581 medical students from two Saudi schools. Frequencies and mean scores of knowledge and attitude were determined. The likelihood of students having adequate knowledge of CRC risk factors and screening modalities was estimated using multivariate logistic regression analysis. Results Knowledge of the risk factors for CRC and screening modalities, and attitude towards screening were poor in 52.47% and 57.83% of the surveyed medical students; respectively. Higher level of medical education (OR=3.23; 95%CI: 2.01-5.18) and a positive attitude towards CRC screening (OR=2.74; 95%CI: 1.86-4.03) were independent predictors of higher knowledge levels. Lack of awareness about CRC and screening modalities among patients, and shortage of specialized healthcare providers were barriers independently associated with low knowledge levels. Conclusions Saudi medical students have limited knowledge of CRC risk factors of and a poor attitude towards CRC screening. These results contribute to our understanding of missed teaching opportunities in Saudi medical schools and suggest intervening at the medical school, clinical practice, and population levels to increase CRC screening practices.


Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 246
Author(s):  
Lasse Kaalby ◽  
Issam Al-Najami ◽  
Ulrik Deding ◽  
Gabriele Berg-Beckhoff ◽  
Robert J. C. Steele ◽  
...  

Fecal hemoglobin (f-Hb) detected by the guaiac fecal occult blood test (gFOBT) may be associated with mortality and cause of death in colorectal cancer (CRC) screening participants. We investigated this association in a randomly selected population of 20,694 participants followed for 33 years. We followed participants from the start of the Hemoccult-II CRC trial in 1985–1986 until December 2018. Data on mortality, cause of death and covariates were retrieved using Danish national registers. We conducted multivariable Cox regressions with time-varying exposure, reporting results as crude and adjusted hazard ratios (aHRs). We identified 1766 patients with at least one positive gFOBT, 946 of whom died in the study period. Most gFOBT-positive participants (93.23%) died of diseases unrelated to CRC and showed higher non-CRC mortality than gFOBT-negative participants (aHR: 1.20, 95% CI 1.10–1.30). Positive gFOBT participants displayed a modest increase in all-cause (aHR: 1.28, 95% CI: 1.18–1.38), CRC (aHR: 4.07, 95% CI: 3.00–5.56), cardiovascular (aHR: 1.22, 95% CI: 1.07–1.39) and endocrine and hematological mortality (aHR: 1.58, 95% CI: 1.19–2.10). In conclusion, we observed an association between positive gFOBT, cause of death and mortality. The presence of f-Hb in the gFOBT might indicate the presence of systemic diseases.


2010 ◽  
Vol 06 (01) ◽  
pp. 51 ◽  
Author(s):  
Gunter Weiss ◽  
Thomas Rösch ◽  
◽  

Despite clear evidence for a better prognosis when detected early, in most countries colorectal cancer (CRC) has a low compliance rate in terms of screening. There are several methods of CRC screening ranging from a variety of stool tests, e.g. faecal occult blood test (FOBT), to endoscopy (sigmoidoscopy, colonoscopy). A blood test for CRC detection is a new alternative, at least for patients not willing to accept screening colonoscopy or to undergo FOBT. The septin 9 biomarker is a potential candidate to fulfil this purpose. It has been validated in several case–control studies, showing a strong association of plasma-containing methylated DNA within the septin 9 gene (mSEPT9) with the presence of CRC. If sensitive methylated-DNA-detection technologies are used formSEPT9 detection in blood plasma samples, sensitivities of about 50% for stage I, 70–80% for stages II and III and 90–100% for stage IV at a specificity of ≥90% have been reported in these studies. Screening experts assume that such a blood-based test will increase compliance to CRC screening. Further studies are ongoing or have just been completed, including a large prospective screening trial involving 8,000 individuals in the US and Germany. The main objectives of this clinical investigation, called Prospective Evaluation of Septin 9 Performance for Colorectal Cancer Screening (PRESEPT), are to determine the performance of the septin 9 test for identification of CRC in a screening population and to demonstrate the health economic benefit of septin 9 in this setting. Results are expected in April 2010. This article presents an update on current analytical and clinical data onmSEPT9.


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253369
Author(s):  
Gemma Ibáñez-Sanz ◽  
Núria Milà ◽  
Carmen Vidal ◽  
Judith Rocamora ◽  
Víctor Moreno ◽  
...  

Introduction The effectiveness of colorectal cancer (CRC) screening programs is directly related to participation and the number of interval CRCs. The objective was to analyse specific-mortality in a cohort of individuals invited to a CRC screening program according to type of CRC diagnosis (screen-detected cancers, interval cancers, and cancers among the non-uptake group). Material and methods Retrospective cohort that included invitees aged 50–69 years of a CRC screening program (target population of 85,000 people) in Catalonia (Spain) from 2000–2015 with mortality follow-up until 2020. A screen-detected CRC was a cancer diagnosed after a positive faecal occult blood test (guaiac or immunochemical); an interval cancer was a cancer diagnosed after a negative test result and before the next invitation to the program (≤24 months); a non-uptake cancer was a cancer in subjects who declined screening. Results A total of 624 people were diagnosed with CRC (n = 265 screen-detected, n = 103 interval cancers, n = 256 non-uptake). In the multivariate analysis, we observed a 74% increase in mortality rate in the group with interval CRC compared to screen-detected CRC adjusted for age, sex, location and stage (HR: 1.74%, 95% CI:1.08–2.82, P = 0.02). These differences were found even when we restricted for advanced-cancers participants. In the stratified analysis for type of faecal occult blood test, a lower mortality rate was only observed among FIT screen-detected CRCs. Conclusion CRC screening with the FIT was associated with a significant reduction in CRC mortality.


2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
I Pereira ◽  
N Kulkarni ◽  
M Dalton ◽  
A Azhar

Abstract Aim There is an increase in the number of complex SPECC cases presented at colorectal MDT meetings with a wide variation in the treatments offered to patients, many of whom undergo high-risk and life-changing surgical resection. This study aimed to evaluate the detection, diagnosis and treatment of early colorectal cancer since the introduction of a SPECC MDT. Method This was a retrospective audit of 108 patients, from the SPECC MDT database from January 2014 to December 2019. Primary outcome assessed the recognition of lesions using endoscopy and radiological evaluation to assess depth of invasion and lymph node involvement. Secondary outcomes included definite treatment, pathological reporting and recurrence. Results Overall, mean age of 72, 79% had one or more significant co-morbidity. Clinical presentation; 61 asymptomatic, 46 symptomatic and 31 referred from the national bowel cancer-screening programme. All patients (n = 108) had endoscopic assessment the lesions were, 53% sessile and 47% pedunculated; 78% of the lesions were found in the rectum. We observed surgical management in 31 cases, endoscopic in 28, chemo-radiotherapy in 12 and 3 cases were palliative. However, 17 (n = 108) underwent failed endoscopic resection and required surgical intervention. Recurrence was observed in 17.6% of cases and mortality in 4%. Conclusions Pathological reports provide a definitive answer to questions of malignancy but SPECC can be challenging in all areas. A specialist MDT allows for appropriate assessment and treatment of lesions and leads to better patient outcomes.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 407-407
Author(s):  
Afsaneh Motamed-Khorasani ◽  
Andrea Lee Small-Howard

407 Background: Routine screening methods for colorectal cancer (CRC) have poor patient compliance and low sensitivity for early stages. The sensitivity rates are 19, 71, 76, and 83% for Fecal Occult Blood test (FOBT), stool DNA test, colonoscopy/sigmoidoscopy, and double-contrast barium enema; respectively. Biological markers have also been tested including CEA (sensitivity of 38.7%); however, its utility in CRC screening is limited due to low sensitivity. Onko-Sure is an FDA-cleared blood test for monitoring of CRC treatment/recurrence. It measures the accumulation of Fibrin/Fibrinogen Degradation products in the serum using anti-DR-70 antibody. The objective was to determine whether DR-70 and CEA combination can improve the sensitivity such that it can be used as a cost-effective alternative to current screening methods yet with a higher patient compliance. Methods: A total of 564 serum samples were retrospectively obtained from a serum bank in two arms: confirmed healthy control (n=298) and biopsy-confirmed CRC (n=266) groups. The samples were tested for DR-70 and CEA. Results: The results showed sensitivity of 58.2% and specificity of 59.83% for DR-70 and CEA combined. The sensitivity for the combined test was 55.5% higher than that of CEA alone. A consistent improvement of sensitivity for the combined usage relative to CEA alone was observed with an increase of 73%, 108%, 58% and 18% in CRC stage I, II, III and IV; respectively. The sensitivity of the combined test was 48%, 47%, 57% and 98% for stages I, II, III and IV. Conclusions: Combining DR-70 and CEA tests showed a significant clinical advantage in CRC screening over using each marker alone. The sensitivity improvement was highest for stages I/II, which has important implications in patient treatment options, prognosis and survival rate due to this early detection. With a 3 times higher sensitivity for early stage CRC compared to using FOBT, this approach should improve the CRC early stage diagnosis. Such early stage detection is less likely using routine approaches for CRC screening because of low sensitivity and low patient compliance.


Author(s):  
José Javier Zamorano-Leon ◽  
Ana López-de-Andres ◽  
Ana Álvarez-González ◽  
Clara Maestre-Miquel ◽  
Paloma Astasio-Arbiza ◽  
...  

Background: In Spain, colorectal cancer screening using the fecal occult blood test, targeted towards the 50–69 age bracket, was implemented on different dates. We aim to assess the temporal trend of colorectal cancer (CRC) screening uptake according to the year of screening implementation in each region and to identify predictors for the uptake of CRC screening. Methods: A cross-sectional study with 12,657 participants from the Spanish National Health Surveys 2011 and 2017 was used. Uptake rates were analyzed according to the date that the screening program was implemented. Results: For regions with programs implemented before 2011, the uptake rate increased 3.34-fold from 2011 to 2017 (9.8% vs. 32.7%; p < 0.001). For regions that implemented screening within the 2011–2016 period, the uptake rose from 4.3% to 13.2% (3.07-fold; p < 0.001), and for regions that implemented screening after 2016, the uptake increased from 3.4% to 8.8% (2.59-fold; p < 0.001). For the entire Spanish population, the uptake increased 3.21-fold (6.8% vs. 21.8%; p < 0.001). Positive predictors for uptake were older age, Spanish nationality, middle-to-high educational level, suffering chronic diseases, non-smoking and living in regions where screening programs were implemented earlier. Conclusions: The different periods for the implementation of CRC screening as well as sociodemographic and health inequalities may have limited the improvement in the screening uptake from 2011 to 2017 in Spain.


2016 ◽  
Vol 25 (4) ◽  
pp. 207-214 ◽  
Author(s):  
Sook Kwin Yong ◽  
Whee Sze Ong ◽  
Gerald Choon-Huat Koh ◽  
Richard Ming Chert Yeo ◽  
Tam Cam Ha

Introduction: This study aims to identify the barriers to adopting faecal occult blood test (FOBT) and colonoscopy as colorectal cancer (CRC) screening methods among the eligible target population of Singapore. Materials and methods: This study was previously part of a randomised controlled trial reported elsewhere. Data was collected from Singapore residents aged 50 and above, via a household sample survey. The study recruited subjects who were aware of CRC screening methods, and interviewed them about the barriers to screening that they faced. Collected results on barriers to each screening method were analysed separately. Results: Out of the 343 subjects, 85 (24.8%) recruited knew about FOBT and/or colonoscopy. Most of the respondents (48.9%) cited not having symptoms as the reason for not using the FOBT. This is followed by inconvenience (31.1%), not having any family history of colon cancer (28.9%), lack of time (28.9%) and lack of reminders/recommendation (28.9%). Of the respondents who indicated not choosing colonoscopy as a screening method, more than one-half (54.8%) identified not having any symptoms as the main barrier for them, followed by not having any family history (38.7%) and having a healthy/low-risk lifestyle (29.0%). There was no difference between the reported barriers to each of the screening methods and the respondents’ dwelling types. Conclusions: Lack of knowledge, particularly the misconceptions of not having symptoms and being healthy, were identified as the main barriers to FOBT and colonoscopy as screening methods. Interventions to increase the uptake of CRC screening in this population should be tailored to address this misconception.


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