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Lotfi E, Kholghi A, Golab F, Mohammadi A, Barati M. Circulating miRNAs and lncRNAs serve as biomarkers for early colorectal cancer diagnosis. Pathol Res Pract 2024; 255:155187. [PMID: 38377721 DOI: 10.1016/j.prp.2024.155187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 01/28/2024] [Accepted: 01/31/2024] [Indexed: 02/22/2024]
Abstract
BACKGROUND Colorectal cancer (CRC), the third most prevalent and lethal disease, accounted for approximately 1.9 million new cases and claimed nearly 861,000 lives in 2018. It is imperative to develop a minimally invasive diagnostic technique for early identification of CRC. This would facilitate the selection of patient populations most suitable for clinical trials, monitoring disease progression, assessing treatment effectiveness, and enhancing overall patient care. Utilizing blood as a biomarker source is advantageous due to its minimal discomfort for patients, enabling better integration into clinical and follow-up trials. Recent findings indicate that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are detectable in the blood of cancer patients, proving crucial in diagnosing various malignancies. METHODS In this case-control study, we collected plasma samples from 30 patients diagnosed with colorectal cancer (CRC) and 30 healthy volunteers. Following RNA extraction, we measured the expression levels of specific biomolecules, including miR-410, miR-211, miR-139, miR-197, lncRNA UICLM, lncRNA FEZF1-AS1, miR-129, lncRNA CCAT1, lncRNA BBOX1-AS1, and lncRNA LINC00698, using real-time quantitative polymerase chain reaction (RT-qPCR). The obtained data underwent analysis using the Mann-Whitney test for non-parametric data and the T-test for parametric data. RESULTS The level of miR-410, miR-211, miR-139, miR-197, lncRNA UICLM, lncRNA FEZF1-AS1 were significantly higher in patients with CRC than healthy controls (p < .05). Meanwhile, the level of miR-129, lncRNA CCAT1, lncRNA BBOX1-AS1, and lncRNA LINC00698 were higher in healthy controls than in CRC patients (p < .05). CONCLUSION MicroRNA (miRNA) and long noncoding RNAs (lncRNAs) have recently emerged as detectable entities in the blood of cancer patients, playing crucial roles in diagnosing various malignancies. However, their specific relevance in the diagnosis of colorectal cancer (CRC) remains underexplored. This study aimed to investigate miRNA and lncRNA profiles in the plasma fraction of human blood to discern significant differences in content and expression levels between CRC patients and healthy individuals. Our cohort comprised 30 CRC patients and 30 healthy controls, with no statistically significant differences (p < 0.05) in age or gender observed between the two groups. Noteworthy is the uniqueness of our study, as we identified a panel of three significant microRNAs and one significant lncRNA, providing a more reliable prediction compared to existing molecular markers in diagnosing CRC. The four genes examined, including miR-211, miR-129, miR-197, and lncRNA UICLM, demonstrated impeccable results in terms of sensitivity and specificity, suggesting their potential candidacy for inclusion in diagnostic panels. Further validation in a larger statistical population is recommended to confirm the robustness of these genes as promising markers for colorectal cancer diagnosis.
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Affiliation(s)
- Ehsan Lotfi
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical sciences, Tehran, Iran
| | - Azam Kholghi
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical sciences, Tehran, Iran
| | - Fereshteh Golab
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Mohammadi
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical sciences, Tehran, Iran
| | - Mahmood Barati
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical sciences, Tehran, Iran.
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Vanthomme K, Rosskamp M, De Schutter H, Vandenheede H. Colorectal cancer incidence and survival inequalities among labour immigrants in Belgium during 2004-2013. Sci Rep 2022; 12:15727. [PMID: 36130977 PMCID: PMC9492689 DOI: 10.1038/s41598-022-19322-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 08/26/2022] [Indexed: 12/02/2022] Open
Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality. We aim to map out differences in CRC incidence and survival between first-generation traditional labour immigrants of Italian, Turkish and Moroccan descent and native Belgians; and assess the contribution of socioeconomic position (SEP) to these differences. Individually-linked data of the 2001 Belgian Census, the Crossroads Bank for Social Security and the Belgian Cancer Registry are used. Age-standardized incidence rates and incidence rate ratios are calculated by country of origin, with and without adjusting for SEP. For CRC patients, 5-year relative survival rates and the relative excess risk for dying within five years after diagnosis are calculated by migrant origin. Lower CRC incidence was observed among immigrants compared to native Belgians, in particular among non-Western immigrants, which could not be explained by SEP. Survival inequalities were less clear, yet, after adjusting for age and stage at diagnosis and educational attainment, we observed a survival advantage among Turkish and Italian immigrant men. Health gains can be made for the native population by adapting lifestyle. The later stage at diagnosis for immigrants is of concern. Barriers regarding screening as perceived by the vulnerable groups should be identified.
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Affiliation(s)
- Katrien Vanthomme
- Sociology Department, Interface Demography, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium.
- Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, C. Heymanslaan 10, 9000, Ghent, Belgium.
| | - Michael Rosskamp
- Research Department, Belgian Cancer Registry, Koningsstraat 215, 1210, Brussels, Belgium
| | - Harlinde De Schutter
- Research Department, Belgian Cancer Registry, Koningsstraat 215, 1210, Brussels, Belgium
| | - Hadewijch Vandenheede
- Sociology Department, Interface Demography, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium
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Kim JI, Fine JP, Sandler DP, Zhao S. Accounting for Preinvasive Conditions in Analysis of Invasive Cancer Risk: Application to Breast Cancer. Epidemiology 2022; 33:48-54. [PMID: 34561346 PMCID: PMC8633059 DOI: 10.1097/ede.0000000000001423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND Preinvasive cancer conditions are often actively treated to minimize progression to life-threatening invasive cancers, but this creates challenges for analysis of invasive cancer risk. Conventional methods of treating preinvasive conditions as censoring events or targeting at the composite outcome could both lead to bias. METHODS We propose two solutions: one that provides exact estimates of risk based on distributional assumptions about progression, and one that provides risk bounds corresponding to extreme cases of no or complete progression. We compare these approaches through simulations and an analysis of the Sister Study data in the context of ductal carcinoma in situ (DCIS) and invasive breast cancer. RESULTS Simulations suggested important biases with conventional approaches, whereas the proposed estimate is consistent when progression parameters are correctly specified, and the risk bounds are robust in all scenarios. With Sister Study, the estimated lifetime risks for invasive breast cancer are 0.220 and 0.269 with DCIS censored or combined. Without detailed progression information, a sensitivity analysis suggested lifetime risk falls between the bounds of 0.214 and 0.269 across assumptions of 10%-95% of DCIS patients progressing to invasive cancer in an average of 1-10 years. CONCLUSIONS When estimating invasive cancer risk while preinvasive conditions are actively treated, it is important to consider the implied assumptions and potential biases of conventional approaches. Although still not perfect, we proposed two practical solutions that provide improved understanding of the underlying mechanism of invasive cancer.
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Affiliation(s)
- Jung In Kim
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences
- Department of Biostatistics, University of North Carolina at Chapel Hill
| | - Jason P. Fine
- Department of Biostatistics, University of North Carolina at Chapel Hill
| | - Dale P. Sandler
- Epidemiology Branch, National Institute of Environmental Health Sciences
| | - Shanshan Zhao
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences
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Hoeck S, van de Veerdonk W, De Brabander I, Kellen E. Does the Flemish colorectal cancer screening programme reach equity in FIT uptake? Eur J Public Health 2020; 29:1108-1114. [PMID: 30887054 DOI: 10.1093/eurpub/ckz043] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND To investigate colorectal cancer (CRC) screening rates by the faecal immunochemical test (FIT) according to sociodemographic characteristics and nationality. METHODS Men and women, aged 56-74, invited to participate in the Flemish CRC screening programme in 2013 and 2014 were included in this study. We analysed the association between CRC screening uptake and sex, age, (first and current) nationality and several proxies for socio-economic status (SES). The statistical analysis was based on descriptive analyses and logistic regression models. RESULTS A total of 1 184 426 persons were included in our analysis. The overall screening uptake was 52.3%, uptake varied by sex, age, nationality and SES. Lower participation rates were associated with the youngest and oldest age categories (56-60 and 70-74) and being male. All nationalities other than Belgian or Dutch were significantly less screened. Lower uptake of screening was also associated with several proxy's for low SES, such as having an allowance for being disabled, not being able to work, being an extended minor and having a social allowance/minimum wage. The descriptive analysis showed a 27% difference in CRC screening uptake between the (early) retired and the people entitled to a minimum wage. CONCLUSIONS There is a significant difference between screening uptake and demographic and socio-economic variables in the first 2 years of the population-based screening programme in Flanders. Based on the study results, implementing strategies to improve participation in those subgroups is needed.
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Affiliation(s)
- S Hoeck
- Centre for Cancer Detection, Bruges, Belgium.,Department of Social Epidemiology and Health Policy, Faculty of Medicine and Health Sciences, University of Antwerp, Belgium
| | - W van de Veerdonk
- Department of Social Epidemiology and Health Policy, Faculty of Medicine and Health Sciences, University of Antwerp, Belgium
| | | | - E Kellen
- Centre for Cancer Detection, Bruges, Belgium.,University Hospital Leuven, Leuven, Belgium
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Do socioeconomic factors play a role in nonadherence to follow-up colonoscopy after a positive faecal immunochemical test in the Flemish colorectal cancer screening programme? Eur J Cancer Prev 2019; 29:119-126. [PMID: 31724969 DOI: 10.1097/cej.0000000000000533] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE In Flanders (Belgium), a population-based colorectal cancer (CRC) screening programme was started in 2013, coordinated by the Centre for Cancer Detection (CCD) in cooperation with the Belgian Cancer Registry (BCR). The CCD offers a biennial faecal immunochemical test (FIT) to Flemish citizens aged 56-74 years and recommends a colonoscopy when screened positive by FIT. The study objective is to investigate sociodemographic differences in follow-up colonoscopy adherence after a positive FIT. METHODS Characteristics of the study population were derived by linkage of data from the CCD and BCR, linked with data of the Intermutualistic Agency and the Crossroads Bank for Social Security, resulting in aggregated tables to ensure anonymity. A total of 37 834 men and women aged 56-74 years with a positive FIT in 2013-2014 were included. Adherence to follow-up colonoscopy was calculated for age, sex, work intensity at household level, preferential reimbursement status, and first and current nationality. Descriptive analyses and logistic regressions were performed. RESULTS Nonadherence to follow-up colonoscopy was associated with increasing age, and was significantly higher in men [odds ratio (OR), 1.08], participants with a preferential reimbursement status (OR, 1.34), very low work intensity (OR, 1.41), no payed work (OR, 1.38) and other than Belgian nationality by birth (OR, 1.6-4.66). CONCLUSION Adherence to follow-up colonoscopy after a positive FIT differs according to sociodemographic variables. Additional research is needed to explore reasons for nonadherence to colonoscopy and tackle barriers by exploring interventions to increase colonoscopy follow-up adherence after a positive FIT in the Flemish colorectal cancer screening programme.
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A Highly Predictive Model for Diagnosis of Colorectal Neoplasms Using Plasma MicroRNA: Improving Specificity and Sensitivity. Ann Surg 2017; 264:575-84. [PMID: 27471839 DOI: 10.1097/sla.0000000000001873] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To develop a plasma-based microRNA (miRNA) diagnostic assay specific for colorectal neoplasms, building upon our prior work. BACKGROUND Colorectal neoplasms [colorectal cancer (CRC) and colorectal advanced adenoma (CAA)] frequently develop in individuals at ages when other common cancers also occur. Current screening methods lack sensitivity, specificity, and have poor patient compliance. METHODS Plasma was screened for 380 miRNAs using microfluidic array technology from a "Training" cohort of 60 patients, (10 each) control, CRC, CAA, breast cancer, pancreatic cancer, and lung cancer. We identified uniquely dysregulated miRNAs specific for colorectal neoplasia (P < 0.05, false discovery rate: 5%, adjusted α = 0.0038). These miRNAs were evaluated using single assays in a "Test" cohort of 120 patients. A mathematical model was developed to predict blinded sample identity in a 150 patient "Validation" cohort using repeat-sub-sampling validation of the testing dataset with 1000 iterations each to assess model detection accuracy. RESULTS Seven miRNAs (miR-21, miR-29c, miR-122, miR-192, miR-346, miR-372, and miR-374a) were selected based upon P value, area under the curve (AUC), fold change, and biological plausibility. Area under the curve (±95% confidence interval) for "Test" cohort comparisons were 0.91 (0.85-0.96) between all neoplasia and controls, 0.79 (0.70-0.88) between colorectal neoplasia and other cancers, and 0.98 (0.96-1.0) between CRC and colorectal adenomas. In our "Validation" cohort, our mathematical model predicted blinded sample identity with 69% to 77% accuracy, 67% to 76% accuracy, and 86% to 90% accuracy for each comparison, respectively. CONCLUSIONS Our plasma miRNA assay and prediction model differentiate colorectal neoplasia from patients with other neoplasms and from controls with higher sensitivity and specificity compared with current clinical standards.
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Decker KM, Demers AA, Nugent Z, Biswanger N, Singh H. Reducing income-related inequities in colorectal cancer screening: lessons learned from a retrospective analysis of organised programme and non-programme screening delivery in Winnipeg, Manitoba. BMJ Open 2016; 6:e009470. [PMID: 26908517 PMCID: PMC4769429 DOI: 10.1136/bmjopen-2015-009470] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE We examined organised colorectal cancer (CRC) screening programme and non-programme faecal occult blood test (FOBT) use from 2008 to 2012 for individuals living in Winnipeg, Manitoba, by area-level income. SETTING Winnipeg, Manitoba, a region with universal healthcare and an organised CRC screening programme. PARTICIPANTS Individuals who had a non-programme FOBT were identified from the Provincial Medical Claims database. Individuals who had a programme FOBT were identified from the provincial screening registry. Census data were used to determine average household income based on area of residence. STATISTICAL ANALYSIS Trends in age-standardised FOBT rates were examined using Joinpoint Regression. Logistic regression was performed to explore the association between programme and non-programme FOBT use and income quintile. RESULTS FOBT use (non-programme and programme) increased from 32.2% in 2008 to 41.6% in 2012. Individuals living in the highest income areas (Q5) were more likely to have a non-programme FOBT compared with those living in other areas. Individuals living in areas with the lowest average income level (Q1) were less likely to have had programme FOBT than those living in areas with the highest average income level (OR 0.80, 95% CI 0.77 to 0.82). There was no difference in programme FOBT use for individuals living in areas with the second lowest income level (Q2) compared with those living in areas with the highest. Individuals living in areas with a moderate-income level (Q3 and Q4) were more likely to have had a programme FOBT compared with those living in an area with the highest income level (OR 1.12, 95% CI 1.09 to 1.15 for Q3 and OR 1.10, 95% CI 1.07 to 1.13 for Q4). CONCLUSIONS Inequities by income observed for non-programme FOBTs were largely eliminated when programme FOBTs were examined. Targeted interventions within organised screening programmes in very low-income areas are needed.
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Affiliation(s)
- Kathleen M Decker
- Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Epidemiology and Cancer Registry, CancerCare Manitoba, Winnipeg, Manitoba, Canada
| | - Alain A Demers
- Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Zoann Nugent
- Department of Internal Medicine, University of Manitoba, Health Sciences Centre, Winnipeg, Manitoba, Canada
- Medical Oncology and Haematology, CancerCare Manitoba, Winnipeg, Manitoba, Canada
| | | | - Harminder Singh
- Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Department of Internal Medicine, University of Manitoba, Health Sciences Centre, Winnipeg, Manitoba, Canada
- Medical Oncology and Haematology, CancerCare Manitoba, Winnipeg, Manitoba, Canada
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Rutter MD, Chattree A, Barbour JA, Thomas-Gibson S, Bhandari P, Saunders BP, Veitch AM, Anderson J, Rembacken BJ, Loughrey MB, Pullan R, Garrett WV, Lewis G, Dolwani S. British Society of Gastroenterology/Association of Coloproctologists of Great Britain and Ireland guidelines for the management of large non-pedunculated colorectal polyps. Gut 2015; 64:1847-73. [PMID: 26104751 PMCID: PMC4680188 DOI: 10.1136/gutjnl-2015-309576] [Citation(s) in RCA: 121] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Revised: 05/25/2015] [Accepted: 05/29/2015] [Indexed: 02/07/2023]
Abstract
These guidelines provide an evidence-based framework for the management of patients with large non-pedunculated colorectal polyps (LNPCPs), in addition to identifying key performance indicators (KPIs) that permit the audit of quality outcomes. These are areas not previously covered by British Society of Gastroenterology (BSG) Guidelines.A National Institute of Health and Care Excellence (NICE) compliant BSG guideline development process was used throughout and the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to structure the guideline development process. A systematic review of literature was conducted for English language articles up to May 2014 concerning the assessment and management of LNPCPs. Quality of evaluated studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist System. Proposed recommendation statements were evaluated by each member of the Guideline Development Group (GDG) on a scale from 1 (strongly agree) to 5 (strongly disagree) with >80% agreement required for consensus to be reached. Where consensus was not reached a modified Delphi process was used to re-evaluate and modify proposed statements until consensus was reached or the statement discarded. A round table meeting was subsequently held to finalise recommendations and to evaluate the strength of evidence discussed. The GRADE tool was used to assess the strength of evidence and strength of recommendation for finalised statements.KPIs, a training framework and potential research questions for the management of LNPCPs were also developed. It is hoped that these guidelines will improve the assessment and management of LNPCPs.
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Affiliation(s)
- Matthew D Rutter
- Department of Gastroenterology, University Hospital of North Tees, Stockton on Tees, UK School of Medicine, Pharmacy and Health, Durham University, Stockton on Tees, UK
| | - Amit Chattree
- School of Medicine, Pharmacy and Health, Durham University, Stockton on Tees, UK
| | - Jamie A Barbour
- Department of Gastroenterology, Queen Elizabeth Hospital, Gateshead, UK
| | | | - Pradeep Bhandari
- Department of Gastroenterology, Queen Alexandra Hospital, Portsmouth, UK
| | | | - Andrew M Veitch
- Department of Gastroenterology, New Cross Hospital, Wolverhampton, UK
| | - John Anderson
- Department of Gastroenterology, Cheltenham General Hospital, Cheltenham, UK
| | | | | | - Rupert Pullan
- Department of Colorectal Surgery, Torbay Hospital, Torquay, UK
| | - William V Garrett
- Department of Colorectal Surgery, Medway Maritime Hospital, Gillingham, UK
| | - Gethin Lewis
- Department of Gastroenterology, University Hospital Llandough, Cardiff, UK
| | - Sunil Dolwani
- Department of Gastroenterology, University Hospital Llandough, Cardiff, UK
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Wang S, Xiang J, Li Z, Lu S, Hu J, Gao X, Yu L, Wang L, Wang J, Wu Y, Chen Z, Zhu H. A plasma microRNA panel for early detection of colorectal cancer. Int J Cancer 2015; 136:152-61. [PMID: 23456911 DOI: 10.1002/ijc.28136] [Citation(s) in RCA: 119] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2012] [Accepted: 02/11/2013] [Indexed: 12/19/2022]
Abstract
Colonoscopy remains the standard screening method for detecting colorectal cancer (CRC) at an early stage. However, many people avoid having a colonoscopy because of the fear for its potential complications. Our study aimed to identify plasma microRNAs for preliminarily screening CRC in general population, so that some unnecessary colonoscopies can be avoided. We investigated plasma microRNA expression in three independent cohorts including the discovery (n = 80), training (n = 112), and validation (n = 49) phases recruited at two medical centers. Microarrays were used for screening 723 microRNAs in 80 plasma samples to identify candidate microRNAs. Quantitative reverse-transcriptase PCR was performed on the 161 training and validation plasma samples to evaluate the candidate microRNAs discovered from microarrays. A logistic regression model was constructed based on the training cohort and then verified by using the validation dataset. Area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified a panel of miR-409-3p, miR-7, and miR-93 that yielded high diagnostic accuracy in discriminating CRC from healthy group (AUC: 0.866 and 0.897 for training and validation dataset, respectively). Moreover, the diagnostic performance of the microRNA panel persisted in nonmetastasis CRC stages (Dukes' A-B, AUC: 0.809 and 0.892 for training and validation dataset, respectively) and in metastasis CRC stages (Dukes' C-D, AUC: 0.917 and 0.865 for training and validation dataset, respectively). In conclusion, our study reveals a plasma microRNA panel that has potential clinical value in early CRC detection and would play a critical role on preliminarily screening CRC in general population.
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Affiliation(s)
- Shuyang Wang
- Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
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Decker KM, Singh H. Reducing inequities in colorectal cancer screening in North America. J Carcinog 2014; 13:12. [PMID: 25506266 PMCID: PMC4253036 DOI: 10.4103/1477-3163.144576] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2014] [Accepted: 10/14/2014] [Indexed: 12/26/2022] Open
Abstract
Colorectal cancer (CRC) is an important cause of mortality and morbidity in North America. Screening using a fecal occult blood test, flexible sigmoidoscopy, or colonoscopy reduces CRC mortality through the detection and treatment of precancerous polyps and early stage CRC. Although CRC screening participation has increased in recent years, large inequities still exist. Minorities, new immigrants, and those with lower levels of education or income are much less likely to be screened. This review provides an overview of the commonly used tests for CRC screening, disparities in CRC screening, and promising methods at the individual, provider, and system levels to reduce these disparities. Overall, to achieve high CRC participation rates and reduce the burden of CRC in the population, a multi-faceted approach that uses strategies at all levels to reduce CRC screening disparities is urgently required.
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Affiliation(s)
- Kathleen M Decker
- Department of Community Health Sciences, University of Manitoba, Canada ; Screening Programs, Cancer Care Manitoba, Canada
| | - Harminder Singh
- Department of Community Health Sciences, University of Manitoba, Canada ; Department of Internal Medicine, University of Manitoba, Canada ; Department of Haematology and Medical Oncology, Cancer Care Manitoba, Canada
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Genetic ancestry is associated with colorectal adenomas and adenocarcinomas in Latino populations. Eur J Hum Genet 2014; 22:1208-16. [PMID: 24518838 DOI: 10.1038/ejhg.2013.310] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Revised: 10/06/2013] [Accepted: 12/05/2013] [Indexed: 12/13/2022] Open
Abstract
Colorectal cancer rates in Latin American countries are less than half of those observed in the United States. Latin Americans are the resultant of generations of an admixture of Native American, European, and African individuals. The potential role of genetic admixture in colorectal carcinogenesis has not been examined. We evaluate the association of genetic ancestry with colorectal neoplasms in 190 adenocarcinomas, 113 sporadic adenomas and 243 age- and sex-matched controls enrolled in a multicentric case-control study in Colombia. Individual ancestral genetic fractions were estimated using the STRUCTURE software, based on allele frequencies and assuming three distinct population origins. We used the Illumina Cancer Panel to genotype 1,421 sparse single-nucleotide polymorphisms (SNPs), and Northern and Western European ancestry, LWJ and Han Chinese in Beijing, China populations from the HapMap project as references. A total of 678 autosomal SNPs overlapped with the HapMap data set SNPs and were used for ancestry estimations. African mean ancestry fraction was higher in adenomas (0.13, 95% confidence interval (95% CI)=0.11-0.15) and cancer cases (0.14, 95% CI=0.12-0.16) compared with controls (0.11, 95% CI=0.10-0.12). Conditional logistic regression analysis, controlling for known risk factors, showed a positive association of African ancestry per 10% increase with both colorectal adenoma (odds ratio (OR)=1.12, 95% CI=0.97-1.30) and adenocarcinoma (OR=1.19, 95% CI=1.05-1.35). In conclusion, increased African ancestry (or variants linked to it) contributes to the increased susceptibility of colorectal cancer in admixed Latin American population.
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Dinh T, Ladabaum U, Alperin P, Caldwell C, Smith R, Levin TR. Health benefits and cost-effectiveness of a hybrid screening strategy for colorectal cancer. Clin Gastroenterol Hepatol 2013; 11:1158-66. [PMID: 23542330 DOI: 10.1016/j.cgh.2013.03.013] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2012] [Revised: 03/05/2013] [Accepted: 03/06/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Colorectal cancer (CRC) screening guidelines recommend screening schedules for each single type of test except for concurrent sigmoidoscopy and fecal occult blood test (FOBT). We investigated the cost-effectiveness of a hybrid screening strategy that was based on a fecal immunological test (FIT) and colonoscopy. METHODS We conducted a cost-effectiveness analysis by using the Archimedes Model to evaluate the effects of different CRC screening strategies on health outcomes and costs related to CRC in a population that represents members of Kaiser Permanente Northern California. The Archimedes Model is a large-scale simulation of human physiology, diseases, interventions, and health care systems. The CRC submodel in the Archimedes Model was derived from public databases, published epidemiologic studies, and clinical trials. RESULTS A hybrid screening strategy led to substantial reductions in CRC incidence and mortality, gains in quality-adjusted life years (QALYs), and reductions in costs, comparable with those of the best single-test strategies. Screening by annual FIT of patients 50-65 years old and then a single colonoscopy when they were 66 years old (FIT/COLOx1) reduced CRC incidence by 72% and gained 110 QALYs for every 1000 people during a period of 30 years, compared with no screening. Compared with annual FIT, FIT/COLOx1 gained 1400 QALYs/100,000 persons at an incremental cost of $9700/QALY gained and required 55% fewer FITs. Compared with FIT/COLOx1, colonoscopy at 10-year intervals gained 500 QALYs/100,000 at an incremental cost of $35,100/QALY gained but required 37% more colonoscopies. Over the ranges of parameters examined, the cost-effectiveness of hybrid screening strategies was slightly more sensitive to the adherence rate with colonoscopy than the adherence rate with yearly FIT. Uncertainties associated with estimates of FIT performance within a program setting and sensitivities for flat and right-sided lesions are expected to have significant impacts on the cost-effectiveness results. CONCLUSIONS In our simulation model, a strategy of annual or biennial FIT, beginning when patients are 50 years old, with a single colonoscopy when they are 66 years old, delivers clinical and economic outcomes similar to those of CRC screening by single-modality strategies, with a favorable impact on resources demand.
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Affiliation(s)
- Tuan Dinh
- Archimedes Inc, San Francisco, California 94105, USA.
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Impact of comorbidity on colorectal cancer screening cost-effectiveness study in diabetic populations. J Gen Intern Med 2012; 27:730-8. [PMID: 22237663 PMCID: PMC3358394 DOI: 10.1007/s11606-011-1972-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2011] [Revised: 12/02/2011] [Accepted: 12/08/2011] [Indexed: 12/18/2022]
Abstract
BACKGROUND Although comorbidity has been shown to affect the benefits and risks of colorectal cancer (CRC) screening, it has not been accounted for in prior cost-effectiveness analyses of CRC screening. OBJECTIVE To evaluate the impact of diagnosis of diabetes mellitus, a highly prevalent comorbidity in U.S. adults aged 50 and older, on health and economic outcomes of CRC screening. DESIGN Cost-effectiveness analysis using an integrated modeling framework. DATA SOURCES Derived from basic and epidemiologic studies, clinical trials, cancer registries, and a colonoscopy database. TARGET POPULATION U.S. 50-year-old population. TIME HORIZON Lifetime. PERSPECTIVE Costs are based on Medicare reimbursement rates. INTERVENTIONS Colonoscopy screening at ten-year intervals, beginning at age 50, and discontinued after age 50, 60, 70, 80 or death. OUTCOME MEASURES Health outcomes and cost effectiveness. RESULTS OF BASE-CASE ANALYSIS Diabetes diagnosis significantly affects cost-effectiveness of CRC screening. For the same CRC screening strategy, a person without diabetes at age 50 gained on average 0.07-0.13 life years more than a person diagnosed with diabetes at age 50 or younger. For a population of 1,000 patients diagnosed with diabetes at baseline, increasing stop age from 70 years to 80 years increased quality-adjusted life years (QALYs) gained by 0.3, with an incremental cost-effectiveness ratio of $206,671/QALY. The corresponding figures for 1,000 patients without diabetes are 2.3 QALYs and $46,957/QALY. RESULTS OF SENSITIVITY ANALYSIS Cost-effectiveness results are sensitive to cost of colonoscopy and adherence to colonoscopy screening. LIMITATIONS Results depend on accuracy of model assumptions. CONCLUSION Benefits of CRC screening differ substantially for patients with and without diabetes. Screening for CRC in patients diagnosed with diabetes at age 50 or younger is not cost-effective beyond age 70. Screening recommendations should be individualized based on the presence of comorbidities.
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Win AK, Macinnis RJ, Hopper JL, Jenkins MA. Risk prediction models for colorectal cancer: a review. Cancer Epidemiol Biomarkers Prev 2011; 21:398-410. [PMID: 22169185 DOI: 10.1158/1055-9965.epi-11-0771] [Citation(s) in RCA: 74] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Risk prediction models are important to identify individuals at high risk of developing the disease who can then be offered individually tailored clinical management, targeted screening and interventions to reduce the burden of disease. They are also useful for research purposes when attempting to identify new risk factors for the disease. In this article, we review the risk prediction models that have been developed for colorectal cancer and appraise their applicability, strengths, and weaknesses. We also discuss the factors to be considered for future development and improvement of models for colorectal cancer risk prediction. We conclude that there is no model that sufficiently covers the known risk factors for colorectal cancer that is suitable for assessment of people from across the full range of risk and that a new comprehensive model is needed.
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Affiliation(s)
- Aung Ko Win
- Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Parkville, Victoria, Australia
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Chu DZJ, Chansky K, Alberts DS, Meyskens FL, Fenoglio-Preiser CM, Rivkin SE, Mills GM, Giguere JK, Goodman GE, Abbruzzese JL, Lippman SM. Adenoma recurrences after resection of colorectal carcinoma: results from the Southwest Oncology Group 9041 calcium chemoprevention pilot study. Ann Surg Oncol 2004; 10:870-5. [PMID: 14527904 DOI: 10.1245/aso.2003.03.037] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Colorectal adenomas are the usual precursors to carcinoma in sporadic and hereditary colorectal cancers (CRC). METHODS A total of 220 CRC patients (stages 0, I, and II) were randomized prospectively in a double-blind pilot study of calcium chemoprevention by using recurrent colorectal adenomas as a surrogate end point. This trial is still in progress, and we report the preliminary findings on adenoma recurrence rates. RESULTS Synchronous adenomas were present in 60% of patients, and cancer confined in a polyp was present in 23% of patients. The overall cumulative adenoma recurrence rate was 31% (19% in the first year, 29% for 2 years, and 35% for 3 years). The recurrence rates were greater for patients with synchronous adenomas: 38% at 3 years (P =.01). Lower stage was associated with higher adenoma recurrence rates (P =.04). Factors including age, sex, site of primary cancer, and whether the cancer was confined to a polyp were not significantly associated with differences in adenoma recurrence rates. CONCLUSIONS The substantial adenoma recurrence rate in patients resected of CRC justifies colonoscopic surveillance on a periodic basis. Patients with higher rates of adenoma recurrences, such as CRC with synchronous adenomas, are ideal subjects for chemoprevention trials.
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Affiliation(s)
- David Z J Chu
- City of Hope National Medical Center, Duarte, California, USA
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Mladen DM, Dragoslav MP, Sanja Z, Bozidar B, Snezana D. Problems in screening colorectal cancer in the elderly. World J Gastroenterol 2003; 9:2335-7. [PMID: 14562405 PMCID: PMC4656490 DOI: 10.3748/wjg.v9.i10.2335] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the problems in the screening of colorectal carcinoma in the elderly.
METHODS: Three models of colorectal cancer prevention were examined: standard screening, active check-up of suspected cases and summons to have endoscopic check-up for previously diagnosed colorectal polyps. The study was performed among three groups of elderly individuals: Group 1 (167 cases), hospitalized asymptomatic individuals without symptoms in large intestines. Group 2 (612 cases): old individuals at home for the aged, out of which 32 showed symptoms of colon disorders; Group 3 (44 cases): elderly people with diagnosed polyps. As a result of 1788 rectosigmoidoscopies, we identified 61 individuals with polyps, out of which 44 patients were over 65 years old. However, only 9 of these 44 individuals agreed to have the endoscopy performed again.
RESULTS: One cancer and 13 polyps were detected in Group 1, and two polyps in Group 2. However, it should be noted that only eleven individuals from Group 2 agreed to have the endoscopy. In Group 3, there were no relapses of the polyps among the nine individuals who came back for the endoscopy.
CONCLUSION: Poor understanding of the screening procedures is one of the greatest problems in early detection of the cancer in the aged. Paradoxically, the cooperation is better with hospitalized patients, than with “successfully old” persons.
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Affiliation(s)
- Davidović M Mladen
- Center of Geriatric Medicine, 11050 Beograd, Rifata Burdzevica 31, Yugoslavia.
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Affiliation(s)
- O Kronborg
- Surgical Department A, Odense University Hospital, Odense, Denmark.
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