AGA Clinical Practice Update on Risk Stratification for Colorectal Cancer Screening and Post-Polypectomy Surveillance: Expert Review

Issaka, Rachel B.; Chan, Andrew T.; Gupta, Samir

doi:10.1053/j.gastro.2023.06.033

Cited by 12 publications

(3 citation statements)

References 94 publications

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“…4 The American Gastroenterological Association recommends that screening for individuals at average-risk for CRC should begin at age 45 years, with a screening colonoscopy every 10 years being the most effective screening modality. 44 However, patient compliance rates remain suboptimal, partly due to complications associated with colonoscopy preparations. 45, 46 Several minimally invasive approaches have been developed to complement screening colonoscopies that could potentially enhance patient compliance, especially those exploiting blood (e.g., SEPT9 promoter methylation) 47 or stool (e.g., FIT, Cologuard).…”

Section: Discussionmentioning

confidence: 99%

Machine learning identifies cell-free DNA 5-hydroxymethylation biomarkers that detect occult colorectal cancer in PLCO Screening Trial subjects

West-Szymanski,

Zhang,

Cui

et al. 2024

Preprint

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BackgroundColorectal cancer (CRC) is a leading cause of cancer-related mortality, and CRC detection through screening improves survival rates. A promising avenue to improve patient screening compliance is the development of minimally-invasive liquid biopsy assays that target CRC biomarkers on circulating cell-free DNA (cfDNA) in peripheral plasma. In this report, we identify cfDNA biomarker candidate genes bearing the epigenetic mark 5-hydroxymethylcytosine (5hmC) that diagnose occult CRC up to 36 months prior to clinical diagnosis using the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial samples.MethodsArchived PLCO Trial plasma samples containing cfDNA were obtained from the National Cancer Institute (NCI) biorepositories. Study subjects included those who were diagnosed with CRC within 36 months of blood collection (i.e., case, n = 201) and those who were not diagnosed with any cancer during an average of 16.3 years of follow-up (i.e., controls, n = 402). Following the extraction of 3 - 8 ng cfDNA from less than 300 microliters plasma, we employed the sensitive 5hmC-Seal chemical labeling approach, followed by next-generation sequencing (NGS). We then conducted association studies and machine-learning modeling to analyze the genome-wide 5hmC profiles within training and validation groups that were randomly selected at a 2:1 ratio.ResultsDespite the technical challenges associated with the PLCO samples (e.g., limited plasma volumes, low cfDNA amounts, and long archival times), robust genome-wide 5hmC profiles were successfully obtained from these samples. Association analyses using the Cox proportional hazards models suggested several epigenetic pathways relevant to CRC development distinguishing cases from controls. A weighted Cox model, comprised of 32-associated gene bodies, showed predictive detection value for CRC as early as 24-36 months prior to overt tumor presentation, and a trend for increased predictive power was observed for blood samples collected closer to CRC diagnosis. Notably, the 5hmC-based predictive model showed comparable performance regardless of sex and self-reported race/ethnicity, and significantly outperformed risk factors such as age and obesity according to BMI (body mass index). Additionally, further improvement of predictive performance was achieved by combining the 5hmC-based model and risk factors for CRC.ConclusionsAn assay of 5hmC epigenetic signals on cfDNA revealed candidate biomarkers with the potential to predict CRC occurrence despite the absence of clinical symptoms or the availability of effective predictors. Developing a minimally-invasive clinical assay that detects 5hmC-modified biomarkers holds promise for improving early CRC detection and ultimately patient survival through higher compliance screening and earlier intervention. Future investigation to expand this strategy to prospectively collected samples is warranted.

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Section: Discussionmentioning

confidence: 99%

Machine learning identifies cell-free DNA 5-hydroxymethylation biomarkers that detect occult colorectal cancer in PLCO Screening Trial subjects

West-Szymanski,

Zhang,

Cui

et al. 2024

Preprint

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“…The study revealed that both age groups had a comparable occurrence of colon adenomas: 14% in the 40-49 age range and 16% in the 50-59 age range [33]. Recently published guidelines by the American Gastroenterological Association (AGA) recommend that individuals carrying mid-risk CRC probability should commence screening protocols at age 45, while individuals having exacerbated CRC risk due to first-degree relative/s developing CRC should commence screening protocols at least 10 years prior to age of CRC development within said relative, or commence screening at age 40 [34].…”

Section: Discussionmentioning

confidence: 99%

Age-Based Comparative Analysis of Colorectal Cancer Colonoscopy Screening Findings

Vilkoite,

Tolmanis,

Abu Meri

et al. 2023

Medicina

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Background and Objectives: Colorectal cancer (CRC) incidence is rapidly emerging among individuals <50 years, termed as early-onset colorectal cancer (EOCRC). This study aimed to probe variations in tumorigenic pathology and relevant manifestations (polyp and adenoma incidence) between suspected cases of EOCRC and late-onset CRC (LOCRC; ≥50 years of age). Materials and Methods: Between September 2022 and February 2023, colonoscopy-based screening data from 1653 patients were included in this study. All eligible participants were divided into two groups, depending upon patient age, where Group 1 consisted of 1021 patients aged <50 years while Group 2 consisted of 632 patients aged ≥ 50 years. Polyp samples were collected when identified peri-procedurally and characterized according to World Health Organization criteria. Results: Polyp detection rate was 42% for the <50-year age group, while this was 76% for the ≥50-year age group. Additionally, the <50-year age group predominated in hyperplastic polyp manifestation, particularly within the rectum and sigmoid colon. In addition, the ≥50-year age group had increased prevalence of serrated polyps and differing adenoma manifestations. Conclusions: This investigation served to highlight the importance of age stratification for CRC colonoscopy-based screening effectiveness, with particular reference to evaluations that are based on polyp localization within differing colon regions.

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“…Presently, two non-invasive screening methods are used: a stool-based test that detects occult blood, namely the guaiac-based fecal occult blood test (gFOBT), and the fecal immunochemical test (FIT). FIT is more sensitive than gFOBT in detecting precancerous lesions and cancer, leading to a strong recommendation for prioritizing FIT over gFOBT [2][3][4][5]. Although FIT is currently the non-invasive test of choice, variability in cutoff levels for positive results leads to inconsistencies in diagnosis and complicates the establishment of a clinical standard [6,7].…”

Section: Introductionmentioning

confidence: 99%

Breath Fingerprint of Colorectal Cancer Patients Based on the Gas Chromatography–Mass Spectrometry Analysis

Kononova,

Mežmale,

Poļaka

et al. 2024

IJMS

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The human body emits a multitude of volatile organic compounds (VOCs) via tissues and various bodily fluids or exhaled breath. These compounds collectively create a distinctive chemical profile, which can potentially be employed to identify changes in human metabolism associated with colorectal cancer (CRC) and, consequently, facilitate the diagnosis of this disease. The main goal of this study was to investigate and characterize the VOCs’ chemical patterns associated with the breath of CRC patients and controls and identify potential expiratory markers of this disease. For this purpose, gas chromatography–mass spectrometry was applied. Collectively, 1656 distinct compounds were identified in the breath samples provided by 152 subjects. Twenty-two statistically significant VOCs (p-xylene; hexanal; 2-methyl-1,3-dioxolane; 2,2,4-trimethyl-1,3-pentanediol diisobutyrate; hexadecane; nonane; ethylbenzene; cyclohexanone; diethyl phthalate; 6-methyl-5-hepten-2-one; tetrahydro-2H-pyran-2-one; 2-butanone; benzaldehyde; dodecanal; benzothiazole; tetradecane; 1-dodecanol; 1-benzene; 3-methylcyclopentyl acetate; 1-nonene; toluene) were observed at higher concentrations in the exhaled breath of the CRC group. The elevated levels of these VOCs in CRC patients’ breath suggest the potential for these compounds to serve as biomarkers for CRC.

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AGA Clinical Practice Update on Risk Stratification for Colorectal Cancer Screening and Post-Polypectomy Surveillance: Expert Review

Cited by 12 publications

References 94 publications

Machine learning identifies cell-free DNA 5-hydroxymethylation biomarkers that detect occult colorectal cancer in PLCO Screening Trial subjects

Machine learning identifies cell-free DNA 5-hydroxymethylation biomarkers that detect occult colorectal cancer in PLCO Screening Trial subjects

Age-Based Comparative Analysis of Colorectal Cancer Colonoscopy Screening Findings

Breath Fingerprint of Colorectal Cancer Patients Based on the Gas Chromatography–Mass Spectrometry Analysis

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