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      A risk-stratified approach to colorectal cancer prevention and diagnosis

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          Abstract

          Population screening and endoscopic surveillance are used widely to prevent the development of and death from colorectal cancer (CRC). However, CRC remains a major cause of cancer mortality and the increasing burden of endoscopic investigations threatens to overwhelm some health services. This Perspective describes the rationale for and approach to improved risk stratification and decision-making for CRC prevention and diagnosis. Limitations of current approaches will be discussed using the UK as an example of the challenges faced by a particular health-care system, followed by discussion of novel risk biomarker utilization. We explore how risk stratification will be advantageous to current health-care providers and users, enabling more efficient use of limited colonoscopy resources. We discuss risk stratification in the setting of population screening as well as the surveillance of high-risk groups and investigation of symptomatic patients. We also address challenges in the development and validation of risk stratification tools and identify key research priorities.

          Abstract

          Population screening and endoscopic surveillance are widely used for colorectal cancer (CRC) prevention and early diagnosis. This Perspective explores the rationale for and approach to risk stratification for CRC prevention and diagnosis, including the limitations, advantages and future challenges for this approach.

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          Most cited references84

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          Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies

          NaNa Keum, Edward Luciano Giovannucci (2019)
          Globally, colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer death. Arising through three major pathways, including adenoma-carcinoma sequence, serrated pathway and inflammatory pathway, CRC represents an aetiologically heterogeneous disease according to subtyping by tumour anatomical location or global molecular alterations. Genetic factors such as germline MLH1 and APC mutations have an aetiologic role, predisposing individuals to CRC. Yet, the majority of CRC is sporadic and largely attributable to the constellation of modifiable environmental risk factors characterizing westernization (for example, obesity, physical inactivity, poor diets, alcohol drinking and smoking). As such, the burden of CRC is shifting towards low-income and middle-income countries as they become westernized. Furthermore, the rising incidence of CRC at younger ages (before age 50 years) is an emerging trend. This Review provides a comprehensive summary of CRC epidemiology, with emphasis on modifiable lifestyle and nutritional factors, chemoprevention and screening. Overall, the optimal reduction of CRC incidence and mortality will require concerted efforts to reduce modifiable risk factors, to leverage chemoprevention research and to promote population-wide and targeted screening.
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            Multitarget Stool DNA Testing for Colorectal-Cancer Screening

            Thomas Imperiale, David F Ransohoff, Steven Itzkowitz … (2014)
            An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening. We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings. Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P=0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P=0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT. In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results. (Funded by Exact Sciences; ClinicalTrials.gov number, NCT01397747.).
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              Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer

              Mingyang Song, Andrew T. Chan, Jun Sun (2019)
              Researchers have discovered associations between elements of the intestinal microbiome (including specific microbes, signaling pathways, and microbiota-related metabolites) and risk of colorectal cancer (CRC). However, it is unclear whether changes in the intestinal microbiome contribute to the development of sporadic CRC or result from it. Changes in the intestinal microbiome can mediate or modify the effects of environmental factors on risk of CRC. Factors that affect risk of CRC also affect the intestinal microbiome, including overweight and obesity; physical activity; and dietary intake of fiber, whole grains, and red and processed meat. These factors alter microbiome structure and function, along with the metabolic and immune pathways that mediate CRC development. We review epidemiologic and laboratory evidence for the influence of the microbiome, diet, and environmental factors on CRC incidence and outcomes. Based on these data, features of the intestinal microbiome might be used for CRC screening and modified for chemoprevention and treatment. Integrated prospective studies are urgently needed to investigate these strategies.
              Article 0 comments Cited 240 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Mark A. Hull:
                ORCID: http://orcid.org/0000-0001-7414-1576
                m.a.hull@leeds.ac.uk
                Journal
                Journal ID (nlm-ta): Nat Rev Gastroenterol Hepatol
                Journal ID (iso-abbrev): Nat Rev Gastroenterol Hepatol
                Title: Nature Reviews. Gastroenterology & Hepatology
                Publisher: Nature Publishing Group UK (London )
                ISSN (Print): 1759-5045
                ISSN (Electronic): 1759-5053
                Publication date (Electronic): 16 October 2020
                Pages: 1-8
                Affiliations
                [1 ]GRID grid.9909.9, ISNI 0000 0004 1936 8403, Leeds Institute of Medical Research at St James’s, , University of Leeds, ; Leeds, UK
                [2 ]GRID grid.1006.7, ISNI 0000 0001 0462 7212, Population Health Sciences Institute, , Newcastle University, ; Newcastle, UK
                Author information
                http://orcid.org/0000-0001-7414-1576
                Article
                Publisher ID: 368
                DOI: 10.1038/s41575-020-00368-3
                PMC ID: 7562765
                PubMed ID: 33067592
                SO-VID: a40cb327-7d63-4315-bbb9-8c34924f42b0
                Copyright © © Springer Nature Limited 2020
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date accepted : 8 September 2020
                Categories
                Subject: Perspective

                Keywords: colonoscopy,risk factors
                Data availability:
                Keywords: colonoscopy, risk factors

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