Dataset Information

Colonoscopic screening shows increased early incidence and progression of adenomas in cystic fibrosis.

ABSTRACT:

Background

Colorectal cancer is an emerging problem in cystic fibrosis (CF). The goal of this study was to evaluate adenoma detection by systematic colonoscopic screening and surveillance.

Methods

We analyzed prospectively collected results of colonoscopies initiated at age 40years from 88 CF patients at a single Cystic Fibrosis Center. We also reviewed results of diagnostic colonoscopies from 27 patients aged 30-39years performed during the same time period at the Center.

Results

The incidence of polyp detection increased markedly after age 40 in CF patients. Greater than 50% were found to have adenomatous polyps; approximately 25% had advanced adenomas as defined by size and/or histopathology; 3% were found to have colon cancer. Multivariate analysis demonstrated specific risk factors for adenoma formation and progression.

Conclusions

Early screening and more frequent surveillance should be considered in patients with CF due to early incidence and progression of adenomas in this patient population.

SUBMITTER: Niccum DE

PROVIDER: S-EPMC5920645 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

Colonoscopic screening shows increased early incidence and progression of adenomas in cystic fibrosis.

Niccum David E DE Billings Joanne L JL Dunitz Jordan M JM Khoruts Alexander A

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 20160202 4

<h4>Background</h4>Colorectal cancer is an emerging problem in cystic fibrosis (CF). The goal of this study was to evaluate adenoma detection by systematic colonoscopic screening and surveillance.<h4>Methods</h4>We analyzed prospectively collected results of colonoscopies initiated at age 40years from 88 CF patients at a single Cystic Fibrosis Center. We also reviewed results of diagnostic colonoscopies from 27 patients aged 30-39years performed during the same time period at the Center.<h4>Resu ...[more]

PMID: 26851188

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Project description:BackgroundLynch syndrome (LS) is associated with germline mutations in DNA mismatch repair (MMR) genes. The first "hit" to inactivate one allele of the predisposing MMR gene is present in every cell, contributing to accelerated tumorigenesis. Less information is available of the nature, timing, and order of other molecular "hits" required for tumor development. To this end, MMR protein expression and coordinated promoter methylation were examined in colorectal specimens prospectively collected from LS mutation carriers (n = 55) during colonoscopy surveillance (10/2011-5/2013), supplemented with retrospective specimens.ResultsLoss of MMR protein corresponding to the gene mutated in the germline increased with dysplasia, with frequency of 0 % in normal mucosa, 50-68 % in low-grade dysplasia adenomas, and 100 % in high-grade dysplasia adenomas and carcinomas. Promoter methylation as a putative "second hit" occurred in 1/56 (2 %) of tumors with silenced MMR protein. A general hypermethylation tendency was evaluated by two gene sets, eight CpG island methylator phenotype (CIMP) genes, and seven candidate tumor suppressor genes linked to colorectal carcinoma (CRC). Hypermethylation followed the same trend as MMR protein loss and was present in some low-grade dysplasia adenomas that still expressed MMR protein suggesting the absence of a "second hit." To assess prospectively collected normal mucosa for carcinogenic "fields," the specimen donors were stratified according to age at biopsy (50 years or below vs. above 50 years) and further according to the absence vs. presence of a (previous or concurrent) diagnosis of CRC. In mutation carriers over 50 years old, two markers from the candidate gene panel (SFRP1 and SLC5A8) revealed a significantly elevated average degree of methylation in individuals with CRC diagnosis vs. those without.ConclusionsOur findings emphasize the importance and early appearance of epigenetic alterations in LS-associated tumorigenesis. The results serve early detection and assessment of progression of CRC.

Dataset Information

Colonoscopic screening shows increased early incidence and progression of adenomas in cystic fibrosis.

Background

Methods

Results

Conclusions

Publications

Colonoscopic screening shows increased early incidence and progression of adenomas in cystic fibrosis.

Similar Datasets

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