Dataset Information

B-RAF mutation and accumulated gene methylation in aberrant crypt foci (ACF), sessile serrated adenoma/polyp (SSA/P) and cancer in SSA/P.

ABSTRACT:

Background

Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor of colon cancer with microsatellite instability (MSI). However, the developmental mechanism of SSA/P remains unknown. We performed genetic analysis and genome-wide DNA methylation analysis in aberrant crypt foci (ACF), SSA/P, and cancer in SSA/P specimens to show a close association between ACF and the SSA/P-cancer sequence. We also evaluated the prevalence and number of ACF in SSA/P patients.

Methods

ACF in the right-side colon were observed in 36 patients with SSA/Ps alone, 2 with cancers in SSA/P, and 20 normal subjects and biopsied under magnifying endoscopy. B-RAF mutation and MSI were analysed by PCR-restriction fragment length polymorphism (RFLP) and PCR-SSCP, respectively, in 15 ACF, 20 SSA/P, and 2 cancer specimens. DNA methylation array analysis of seven ACF, seven SSA/P, and two cancer in SSA/P specimens was performed using the microarray-based integrated analysis of methylation by isochizomers (MIAMI) method.

Results

B-RAF mutations were frequently detected in ACF, SSA/P, and cancer in SSA/P tissues. The number of methylated genes increased significantly in the order of ACFConclusionsOur results suggest that ACF are precursor lesions of the SSA/P-cancer sequence in patients with SSA/P, where ACF arise by B-RAF mutation and methylation of some of the six identified genes and develop into SSA/Ps through accumulated methylation of these genes.

SUBMITTER: Inoue A

PROVIDER: S-EPMC4453443 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Publications

B-RAF mutation and accumulated gene methylation in aberrant crypt foci (ACF), sessile serrated adenoma/polyp (SSA/P) and cancer in SSA/P.

Inoue A A Okamoto K K Fujino Y Y Nakagawa T T Muguruma N N Sannomiya K K Mitsui Y Y Takaoka T T Kitamura S S Miyamoto H H Okahisa T T Fujimori T T Imoto I I Takayama T T

British journal of cancer 20141014 2

<h4>Background</h4>Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor of colon cancer with microsatellite instability (MSI). However, the developmental mechanism of SSA/P remains unknown. We performed genetic analysis and genome-wide DNA methylation analysis in aberrant crypt foci (ACF), SSA/P, and cancer in SSA/P specimens to show a close association between ACF and the SSA/P-cancer sequence. We also evaluated the prevalence and number of ACF in SSA/P patients.<h4>Methods</h4>AC ...[more]

PMID: 25314065

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Project description:ImportanceResearch demonstrates adenoma detection rate (ADR) and proximal sessile serrated polyp detection rate (pSSPDR) are associated with endoscopist characteristics including sex, specialty, and years in practice. However, many studies have not adjusted for other risk factors associated with colonic neoplasia.ObjectiveTo assess the association between endoscopist characteristics and polyp detection after adjusting the factors included in previous studies as well as other factors.Design, setting, and participantsThis cohort study was conducted in the Cleveland Clinic health system with data from individuals undergoing screening colonoscopies between January 2015 and June 2017. The study analyzed data using methods from previous studies that have demonstrated significant associations between endoscopist characteristics and ADR or pSSPDR. Multilevel mixed-effects logistic regression was performed to examine 7 endoscopist characteristics associated with ADRs and pSSPDRs after controlling for patient demographic, clinical, and colonoscopy-associated factors.ExposuresSeven characteristics of endoscopists performing colonoscopy.Main outcomes and measuresThe ADR and pSSPDR, with a hypothesis created after data collection began.ResultsA total of 16 089 colonoscopies were performed in 16 089 patients by 56 clinicians. Of these, 8339 patients were male (51.8%), and the median (range) age of the cohort was 59 (52-66) years. Analyzing the data by the methods used in 4 previous studies yielded an association between endoscopist and polyp detection; surgeons (OR, 0.49 [95% CI, 0.28-0.83]) and nongastroenterologists (OR, 0.50 [95% CI 0.29-0.85]) had reduced odds of pSSPDR, which was similar to results in previous studies. In a multilevel mixed-effects logistic regression analysis, ADR was not significantly associated with any endoscopist characteristic, and pSSPDR was only associated with years in practice (odds ratio, 0.86 [95% CI, 0.83-0.89] per increment of 10 years; P < .001) and number of annual colonoscopies performed (odds ratio, 1.05 [95% CI, 1.01-1.09] per 50 colonoscopies/year; P = .02).Conclusions and relevanceThe differences in ADRs that were associated with 7 of 7 endoscopist characteristics and differences in pSSPDRs that were associated with 5 of 7 endoscopist characteristics in previous studies may have been associated with residual confounding, because they were not replicated in this analysis. Therefore, these characteristics should not influence the choice of endoscopist for colorectal cancer screening. However, clinicians further from their training and those with lower colonoscopy volumes have lower adjusted pSSPDRs and may need additional training to help increase pSSPDRs.

Project description:BackgroundRemoval of colorectal polyps during screening could reduce the incidence of colorectal cancer (CRC). However, there is a lack of data on risk factors associated with recurrence of polyps, including conventional adenomas and serrated polyps (SPs). This study aimed to determine risk factors for recurrence of colorectal polyps and their subtypes based on the characteristics of the patients and polyps.MethodsA total of 1,165 patients diagnosed with conventional adenoma or SP in the Sixth Affiliated Hospital of Sun Yat-sen University between January 2013 and December 2019 were enrolled in this study, including 668 cases with conventional adenomas, 385 with SPs, and 112 with coexistence of adenomas and SPs. Univariate analysis and multivariate logistic regression were used to identify potential risk factors for polyp recurrence. A nomogram was established according to risk factors and the performance was evaluated using calibration plots.ResultsDuring a median follow-up of 24 months, recurrent polyps were observed in 531 (45.6%) cases. Male, age ≥50 years, body mass index (BMI) ≥24 kg/m2, at least three polyps, smoking, alcohol consumption, family history of polyps, and family history of CRC were independent risk factors for polyp recurrence. The Harrell's C-index of the nomogram developed with these parameters was 0.69 and the calibration plots showed good agreement between actual polyp recurrence and nomogram-predicted recurrence probability. In the subtype analyses, conventional adenomas had the same risk factors for recurrence as all polyps, while smoking, alcohol consumption, family history of polyps, and family history of CRC were not risk factors for SP recurrence.ConclusionsWe identified several risk factors for recurrence of colorectal polyps and found that some of them could increase the risk of adenoma recurrence but not SP recurrence, including smoking, alcohol consumption, and family history of polyps/CRC, which might help us to understand different etiology and biology between conventional adenomas and SPs.

Dataset Information

B-RAF mutation and accumulated gene methylation in aberrant crypt foci (ACF), sessile serrated adenoma/polyp (SSA/P) and cancer in SSA/P.

Background

Methods

Results

Publications

B-RAF mutation and accumulated gene methylation in aberrant crypt foci (ACF), sessile serrated adenoma/polyp (SSA/P) and cancer in SSA/P.

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