Metabolic unhealthiness is an important predictor for the development of advanced colorectal neoplasia.
Ontology highlight
ABSTRACT:
SUBMITTER: Kim TJ
PROVIDER: S-EPMC5566381 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Following colonoscopic polypectomy, US Multisociety Task Force (USMSTF) guidelines stratify patients based on risk of subsequent advanced neoplasia (AN) using number, size, and histology of resected polyps, but have only moderate sensitivity and specificity. We hypothesized that a state-of-the-art statistical prediction model might improve identification of patients at high risk of future AN and address these challenges.Data were pooled from seven prospective studies which had follow-up ascertainment of metachronous AN within 3-5 years of baseline polypectomy (combined n = 8,228). Pooled data were randomly split into training (n = 5,483) and validation (n = 2,745) sets. A prognostic model was developed using best practices. Two risk cut-points were identified in the training data which achieved a 10 percentage point improvement in sensitivity and specificity, respectively, over current USMSTF guidelines. Clinical benefit of USMSTF versus model-based risk stratification was then estimated using validation data.The final model included polyp location, prior polyp history, patient age, and number, size and histology of resected polyps. The first risk cut-point improved sensitivity but with loss of specificity. The second risk cut-point improved specificity without loss of sensitivity (specificity 46.2 % model vs. 42.1 % guidelines, p < 0.001; sensitivity 75.8 % model vs. 74.0 % guidelines, p = 0.64). Estimated AUC was 65 % (95 % CI: 62-69 %).This model-based approach allows flexibility in trading sensitivity and specificity, which can optimize colonoscopy over- versus underuse rates. Only modest improvements in prognostic power are possible using currently available clinical data. Research considering additional factors such as adenoma detection rate for risk prediction appears warranted.
| S-EPMC5495135 | biostudies-literature
Project description:BACKGROUND: It is uncertain whether synchronous colorectal cancers (S-CRCs) preferentially develop through widespread DNA methylation and whether they have a prognosis worse than solitary CRC. As tumours with microsatellite instability (MSI) may confound the effect of S-CRC methylation on outcome, we addressed this issue in a series of CRC characterised by BRAF and MS status. METHODS: Demographics, clinicopathological records and disease-specific survival (DSS) were assessed in 881 consecutively resected CRC undergoing complete colonoscopy. All tumours were typed for BRAF(c.1799T>A) mutation and MS status, followed by search of germ-line mutation in patients with MSI CRC. RESULTS: Synchronous colorectal cancers (50/881, 5.7%) were associated with stage IV microsatellite-stable (MSS) CRC (19/205, 9.3%, P=0.001) and with HNPCC (9/32, 28%, P<0.001). BRAF mutation (60/881, 6.8%) was associated with sporadic MSI CRC (37/62, 60%, P<0.001) but not with S-CRC (3/50, 6.0%, P=0.96). Synchronous colorectal cancer (HR 1.82; 95% CI 1.15-2.87; P=0.01), synchronous advanced adenoma (HR 1.81; 95% CI 1.27-2.58; P=0.001), and BRAF(c.1799T>A) mutation (HR 2.16; 95% CI 1.25-3.73; P=0.01) were stage-independent predictors of death from MSS CRC. Disease-specific survival of MSI CRC patients was not affected by S-CRC (HR 0.74; 95% CI 0.09-5.75; P=0.77). CONCLUSION: Microsatellite-stable CRCs have a worse prognosis if S-CRC or synchronous advanced adenoma are diagnosed. The occurrence and the enhanced aggressiveness of synchronous MSS advanced neoplasia are not associated with BRAF mutation.
| S-EPMC3950856 | biostudies-other
Project description:PurposeBRAF mutation and DNA hypermethylation have linked sessile serrated adenomas/polyps (SSA/Ps) to serrated colorectal cancer (CRC) in cross-sectional studies, but they have not been evaluated in a longitudinal study. We aimed to evaluate the associations between molecular markers of serrated polyps and subsequent advanced colorectal neoplasia.MethodsStudy subjects included Kaiser Permanente Washington members aged 20-75 years who received an index colonoscopy between 1/1/1998 and 12/31/2007 and had hyperplastic polyps (HPs) or SSA/Ps according to study pathology review. Polyps from index colonoscopies were removed and assayed for BRAF mutation, CpG island methylator phenotype (CIMP), and MLH1 methylation. Pathology reports and biopsies from the subsequent lower gastrointestinal endoscopy through 1/1/2013 were reviewed for advanced colorectal neoplasia. We identified additional incident CRC cases through linkage to the Seattle-Puget Sound Surveillance Epidemiology and End Results registry. We used generalized estimating equations to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for subsequent advanced colorectal neoplasia, comparing index serrated polyps with different molecular markers.ResultsWe included 553 individuals with index serrated polyps (420 HPs and 133 SSA/Ps) and 795 subsequent endoscopies. The prevalence of BRAF-mutant, CIMP-high, and MLH1-methylated serrated polyps were 51%, 4%, and 2%, respectively. BRAF and CIMP were not associated with subsequent advanced colorectal neoplasia. MLH1-methylated SSP/As were significantly more likely to have subsequent advanced neoplasia (OR = 4.66, 95% CI 1.06-20.51).ConclusionOur results suggest that BRAF-mutant and CIMP-high serrated polyps are not associated with subsequent advanced colorectal neoplasia. Among SSA/Ps, MLH1 methylation may be an important marker to identify high-risk CRC precursors.
| S-EPMC8259952 | biostudies-literature
Project description:PurposeColorectal cancer (CRC) screening guidelines recommend increased surveillance of individuals with sessile serrated adenomas/polyps (SSA/Ps), but there is uncertainty about the risk associated with SSA/Ps. We aimed to determine the association between SSA/Ps and subsequent advanced colorectal neoplasia.MethodsThis case-control study included Kaiser Permanente Washington (KPWA) members who received an index colonoscopy between 1/1/1998 and 12/31/2007, and had hyperplastic polyps (HPs) or SSA/Ps but no conventional adenomas according to study pathologist histologic review. Subsequent pathology reports and biopsies through 1/1/2013 were reviewed for advanced colorectal neoplasia. We linked to the Seattle-Puget Sound Surveillance Epidemiology and End Results (SEER) registry to identify additional CRC cases. We used generalized estimating equations with a logit link to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for advanced colorectal neoplasia, comparing those with SSA/Ps to those with HPs.ResultsThere were 161 individuals with index SSA/Ps, 548 with HPs, and 918 subsequent endoscopies included in analyses. Of those with index SSA/Ps, 19 had subsequent advanced colorectal neoplasia; 39 with HPs had subsequent advanced colorectal neoplasia. Compared to those with HPs, those with SSA/Ps were not statistically significantly more likely to have subsequent advanced colorectal neoplasia (adjusted OR 1.79; CI 0.98-3.28). Polyp size ≥ 10 mm, right colon location, and the presence of multiple serrated polyps were also not associated with advanced colorectal neoplasia.ConclusionsOur results suggest that there is not a strong association between SSA/Ps and subsequent advanced colorectal neoplasia during the 5 years following SSA/P removal.
| S-EPMC6736607 | biostudies-literature
Project description:BackgroundColorectal cancer (CRC) is one of the leading causes of cancer related morbidity and death. Despite the fact that the mean age at diagnosis of CRC is lower in men, screening by colonoscopy or fecal occult blood test (FOBT) is initiated at same age in both genders. The prevalence of the common CRC precursor lesion, advanced adenoma, is well documented only in the screening population. The purpose of this study was to assess the risk of advanced adenoma at ages below screening age.Methods and findingsWe analyzed data from a census of 625,918 outpatient colonoscopies performed in adults in Bavaria between 2006 and 2008. A logistic regression model to determine gender- and age-specific risk of advanced neoplasia was developed. Advanced neoplasia was found in 16,740 women (4.6%) and 22,684 men (8.6%). Male sex was associated with an overall increased risk of advanced neoplasia (odds ratio 1.95; 95% confidence interval, CI, 1.91 to 2.00). At any age and in any indication group, more colonoscopies were needed in women than in men to detect advanced adenoma or cancer. At age 75 14.8 (95% CI, 14.4-15.2) screening, 18.2 (95% CI, 17.7-18.7) diagnostic, and 7.9 (95% CI, 7.6-8.2) colonoscopies to follow up on a positive FOBT (FOBT colonoscopies) were needed to find advanced adenoma in women. At age 50 39.0 (95% CI, 38.0-40.0) diagnostic, and 16.3 (95% CI, 15.7-16.9) FOBT colonoscopies were needed. Comparable numbers were reached 20 and 10 years earlier in men than in women, respectively.ConclusionsAt any age and independent of the indication for colonoscopy, men are at higher risk of having advanced neoplasia diagnosed upon colonoscopy than women. This suggests that starting screening earlier in life in men than in women might result in a relevant increase in the detection of asymptomatic preneoplastic and neoplastic colonic lesions.
| S-EPMC3101231 | biostudies-literature
Project description:Eliciting patient preferences within the context of shared decision making has been advocated for colorectal cancer screening. Risk stratification for advanced colorectal neoplasia (ACN) might facilitate more effective shared decision making when selecting an appropriate screening option. Our objective was to develop and validate a clinical index for estimating the probability of ACN at screening colonoscopy.We conducted a cross-sectional analysis of 3,543 asymptomatic, mostly average-risk patients 50-79 years of age undergoing screening colonoscopy at two urban safety net hospitals. Predictors of ACN were identified using multiple logistic regression. Model performance was internally validated using bootstrapping methods.The final index consisted of five independent predictors of risk (age, smoking, alcohol intake, height, and a combined sex/race/ethnicity variable). Smoking was the strongest predictor (net reclassification improvement (NRI), 8.4%) and height the weakest (NRI, 1.5%). Using a simplified weighted scoring system based on 0.5 increments of the adjusted odds ratio, the risk of ACN ranged from 3.2% (95% confidence interval (CI), 2.6-3.9) for the low-risk group (score ?2) to 8.6% (95% CI, 7.4-9.7) for the intermediate/high-risk group (score 3-11). The model had moderate to good overall discrimination (C-statistic, 0.69; 95% CI, 0.66-0.72) and good calibration (P=0.73-0.93).A simple 5-item risk index based on readily available clinical data accurately stratifies average-risk patients into low- and intermediate/high-risk categories for ACN at screening colonoscopy. Uptake into clinical practice could facilitate more effective shared decision-making for CRC screening, particularly in situations where patient and provider test preferences differ.
| S-EPMC4705553 | biostudies-literature
Project description:Ulcerative colitis-associated neoplasia (UCAN) harbors unique genetic alterations and mutational tendencies. The clinical application of gene panel testing enables precision medicine by tailoring treatment to individual gene alterations. We hypothesized that gene panel testing may detect clinically important genetic alterations in UCAN, with potential usefulness for the diagnosis and treatment of UCAN. In the present study, gene panel testing was used to identify genetic alterations in UCAN, and the possibility of clinical utility of gene panel testing in UCAN was investigated. The present study included 15 patients with UCAN, and gene panel testing was performed to identify genetic alterations associated with diagnosis and treatment. Genetic alterations of UCAN were compared with those of 203 patients with sporadic colorectal cancer (CRC). APC and PTEN mutations were less frequent, while RNF43 frameshift or nonsense mutations were more frequent in UCAN compared with sporadic CRC. TP53 mutations were identified in 13/15 patients (87%) with UCAN. Notably, 4/15 patients (27%) with UCAN had no genetic alterations other than TP53 mutation, while this occurred in 1/203 patients (0.5%) with sporadic CRC (P<0.001). Microsatellite instability-high was identified in 2/15 patients (13%) with UCAN. Mutational signature 3, which is associated with homologous recombination deficiency, was detected in 14/15 patients (93%) with UCAN, and enriched in UCAN compared with sporadic CRC (P=0.030). In conclusion, gene panel testing can detect important genetic alterations that can be useful for diagnosis and treatment in UCAN, and may provide clinicians with important information for tailored treatment strategies.
| S-EPMC9641802 | biostudies-literature
Project description:BACKGROUND:Colorectal cancer (CRC) is a common and potentially preventable malignancy. Evidence has emerged that coronary artery disease patients are at increased risk for developing CRC by shared risk factors. Here we investigated an association between CRC and atrial fibrillation (AF), a surrogate marker of cardiovascular risk, in the setting of routine screening colonoscopy. METHODS:We investigated 1949 asymptomatic participants (median age 61 [54-67] years, 49% females) undergoing screening colonoscopy within the SAKKOPI registry (Salzburg Colon Cancer Prevention Initiative). Forty-six participants with AF (2.4%) were identified, and colonoscopy findings were compared to non-AF participants. Propensity Score Matching (PSM) was used to create 1:1 and 3:1 age- and gender-matched couples. RESULTS:Abnormal findings on screening colonoscopy (any form of adenoma or carcinoma) were more common in AF participants with an odds ratios (OR) of 2.4 [1.3-4.3] in the unmatched analysis, and 2.6 [1.1-6.3] and 2.0 [1.1-4.0] in the 1:1 and 3:1 matched groups, respectively. Correspondingly, the odds of finding advanced adenomas or carcinomas was elevated about three-fold across the different matched and unmatched analyses (OR 3.3 [1.1-10.8] for 3:1 matched participants). At the same time, the prevalence and number of colonic lesions were significantly higher in AF participants (63.0% vs. 33.4% for 3:1 matched participants, p < 0.001). Non-CRC related findings on colonoscopy, like diverticulosis, were non-different between groups. CONCLUSION:Participants with AF had a higher burden of advanced premalignant adenomas and CRC in routine colonoscopy screening. Our data suggest that practitioners should monitor the CRC screening status, especially in AF patients.
| S-EPMC6678897 | biostudies-other
Project description:Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Although noninvasive stool-based screening tests are used for the early detection of colorectal neoplasia, concerns have been raised about their sensitivity and specificity. A metabolomics-based approach provides a potential noninvasive strategy to identify biomarkers of colorectal carcinogenesis including premalignant adenomas. Our primary objective was to determine whether a distinct metabolic profile could be found in both feces and plasma during experimental colorectal carcinogenesis. Feces, plasma as well as tumor tissue and normal colorectal mucosa were obtained from A/J mice at several time points following administration of azoxymethane or saline. Ultra-performance liquid chromatography tandem mass spectroscopy and gas chromatography mass spectroscopy were used to quantify metabolites in each of these matrices. Here, we show that colorectal carcinogenesis was associated with significant metabolic alterations in both the feces and plasma, some of which overlap with metabolic changes in the tumor tissue. These consisted of 33 shared changes between feces and tumor, 14 shared changes between plasma and tumor, and 3 shared changes across all 3 matrices. For example, elevated levels of sarcosine were found in both tumor and feces whereas increased levels of 2-hydroxyglutarate were found in both tumor and plasma. Collectively, these results provide evidence that metabolomics can be used to detect changes in feces and plasma during azoxymethane-induced colorectal carcinogenesis and thus provide a strong rationale for future studies in humans.
| S-EPMC3518611 | biostudies-literature
Project description:BACKGROUND:Guidelines from the United Kingdom and the United States on risk stratification after polypectomy differ, as do recommended surveillance intervals. OBJECTIVE:To compare risk for advanced colorectal neoplasia at 1-year colonoscopy among patients cross-classified by U.S. and U.K. surveillance guidelines. DESIGN:Pooled analysis of 4 prospective studies between 1984 and 1998. SETTING:Academic and private clinics in the United States. PATIENTS:3226 postpolypectomy patients with 6- to 18-month follow-up colonoscopy. MEASUREMENTS:Rates of advanced neoplasia (an adenoma ?1 cm, high-grade dysplasia, >25% villous architecture, or invasive cancer) at 1 year, compared across U.S. and U.K. risk categories. RESULTS:Advanced neoplasia was detected 1 year after polypectomy in 3.8% (95% CI, 2.7% to 4.9%) of lower-risk patients and 11.2% (CI, 9.8% to 12.6%) of higher-risk patients by U.S. criteria. According to U.K. criteria, 4.4% (CI, 3.3% to 5.4%) of low-risk patients, 9.9% (CI, 8.3% to 11.5%) of intermediate-risk patients, and 18.7% (CI, 14.8% to 22.5%) of high-risk patients presented with advanced neoplasia; U.K. high-risk patients comprised 12.1% of all patients. All U.S. lower-risk patients were low-risk by U.K. criteria; however, more patients were classified as low-risk, because the U.K. guidelines do not consider histologic features. Higher-risk U.S. patients were distributed across the 3 U.K. categories. Among all patients with advanced neoplasia, 26.3% were reclassified by the U.K. criteria to a higher-risk category and 7.0% to a lower-risk category, with a net 19.0% benefiting from detection 2 years earlier. Overall, substitution of U.K. for U.S. guidelines resulted in an estimated 0.03 additional colonoscopy every 5 years per patient. LIMITATIONS:Patients were enrolled 15 to 20 years ago, and quality measures for colonoscopy were unavailable. Patients lacking follow-up colonoscopy or with surveillance colonoscopy after 6 to 18 months and those with cancer or insufficient baseline adenoma characteristics were excluded (2076 of 5302). CONCLUSION:Application of the U.K. guidelines in the United States could identify a subset of high-risk patients who may warrant a 1-year clearing colonoscopy without substantially increasing rates of colonoscopy. PRIMARY FUNDING SOURCE:European Union Public Health Programme.
| S-EPMC3787691 | biostudies-literature