Increased prevalence of colonic adenomas in patients with cystic fibrosis

Hegagi, Mehdi; Aaron, Shawn D.; James, Paul D.; Goel, Rakesh; Chatterjee, Avijit

doi:10.1016/j.jcf.2017.07.009

Cited by 12 publications

(10 citation statements)

References 14 publications

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“…The risk increase was similar to rates published previously [4]. The challenges faced in this study, namely poor uptake of the screening measure and difficulty with prep in those who did move forward with the study offer clinicians insight to potential barriers to implementation of the new guidelines [7].…”

supporting

confidence: 82%

New Comorbidities in the Changing Face of Cystic Fibrosis Care

Bonk

Rey

Hadjiliadis

2017

Journal of Cystic Fibrosis

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supporting

confidence: 82%

New Comorbidities in the Changing Face of Cystic Fibrosis Care

Bonk

Rey

Hadjiliadis

2017

Journal of Cystic Fibrosis

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“…No signatures of inflammation were found in our study when compared to the genes enriched in Crohn's disease (CD) patients with inflammation [52]. This further suggests a potential mechanism underlying the reported increased risk and early development of colon cancer in CF patients [5,66].…”

Section: Discussionmentioning

confidence: 50%

“…Recent advances in treatment have significantly prolonged the lives of CF patients [65]. However, this has led to new challenges, such as an elevated risk for gastrointestinal cancer [66]. Thus, CF patients show 5-10-fold increased risk of CRC compared to healthy individuals and that increases even further with immunosuppressive drugs [3,6].…”

Section: Discussionmentioning

confidence: 99%

Interactions between the gut microbiome and host gene regulation in cystic fibrosis

et al. 2020

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Background: Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasians. It is caused by mutations in the CFTR gene, leading to poor hydration of mucus and impairment of the respiratory, digestive, and reproductive organ functions. Advancements in medical care have led to markedly increased longevity of patients with cystic fibrosis, but new complications have emerged, such as early onset of colorectal cancer. Although the pathogenesis of colorectal cancer in cystic fibrosis remains unclear, altered host-microbe interactions might play a critical role. To investigate this, we characterized changes in the microbiome and host gene expression in the colonic mucosa of cystic fibrosis patients relative to healthy controls, and identified host gene-microbiome interactions in the colon of cystic fibrosis patients. Methods: We performed RNA-seq on colonic mucosa samples from cystic fibrosis patients and healthy controls to determine differentially expressed host genes. We also performed 16S rRNA sequencing to characterize the colonic mucosal microbiome and identify gut microbes that are differentially abundant between patients and healthy controls. Lastly, we modeled associations between relative abundances of specific bacterial taxa in the gut mucosa and host gene expression. Results: We find that 1543 genes, including CFTR, show differential expression in the colon of cystic fibrosis patients compared to healthy controls. These genes are enriched with functions related to gastrointestinal and colorectal cancer, such as metastasis of colorectal cancer, tumor suppression, p53, and mTOR signaling pathways. In addition, patients with cystic fibrosis show decreased gut microbial diversity, decreased abundance of butyrate producing bacteria, such as Ruminococcaceae and Butyricimonas, and increased abundance of other taxa, such as Actinobacteria and Clostridium. An integrative analysis identified colorectal cancer-related genes, including LCN2 and DUOX2, for which gene expression is correlated with the abundance of colorectal cancer-associated bacteria, such as Ruminococcaceae and Veillonella. Conclusions: In addition to characterizing host gene expression and mucosal microbiome in cystic fibrosis patients, our study explored the potential role of host-microbe interactions in the etiology of colorectal cancer in cystic fibrosis. Our results provide biomarkers that may potentially serve as targets for stratifying risk of colorectal cancer in patients with cystic fibrosis.

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“…Recent advances in the treatment have significantly prolonged the lives of CF patients [67,68]. However, this led to new challenges, such as an elevated risk for gastrointestinal cancer [2,69]. Thus, CF patients show 5-10-fold increased risk of CRC compared to healthy individuals, and that increases even further with immunosuppressive drugs [3,6].…”

Section: Discussionmentioning

confidence: 99%

“…Down-regulation of these tumor suppressor genes can lead to predisposition of colon cancer [42,76,77], suggesting a potential mechanism underlying the reported increased risk and early development of colon cancer in CF patients [5,69].…”

Section: Discussionmentioning

confidence: 99%

Interactions between the gut microbiome and host gene regulation in cystic fibrosis

Dayama

Priya

Niccum

et al. 2019

Preprint

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Cystic Fibrosis (CF) is the most common autosomal recessive genetic disease in Caucasians. It is caused by mutations in the CFTR gene, leading to poor hydration of mucus and impairment of the respiratory, digestive, and reproductive organ functions.Advancements in medical care have lead to markedly increased longevity of patients with CF, but new complications have emerged, such as early onset of colorectal cancer (CRC). Although the pathogenesis of CRC in CF remains unclear, altered host-microbe interactions might play a critical role. Here, we characterize the changes in the gut microbiome and host gene expression in colonic mucosa of CF patients relative to healthy controls. We find that CF patients show decreased microbial diversity, decreased abundance of taxa such as Butyricimonas, Sutterella, and Ruminococcaceae, and increased abundance of other taxa, such as Actinobacteria and Firmicutes. We find that 1543 genes, including CFTR, show differential expression in 2 the colon of CF patients compared to healthy controls. Interestingly, we find that these genes are enriched with functions related to gastrointestinal and colorectal cancer, such as metastasis of CRC, tumor suppression, cellular dysfunction, p53 and mTOR signaling pathways. Lastly, we modeled associations between relative abundances of specific bacterial taxa in the gut mucosa and host gene expression, and identified CRCrelated genes, including LCN2 and DUOX2, for which gene expression is correlated with the abundance of CRC-associated bacteria, such as Ruminococcaceae and Veillonella. Our results provide new insight into the role of host-microbe interactions in the etiology of CRC in CF. colorectal cancer.progress faster to more advanced neoplasms [4]. In fact, loss of CFTR expression in tumors of non-CF patients has been associated with a worse prognosis in early stage CRC [5]. Recently, specific recommendations for CRC screening were introduced in standard care of adult CF patients, which include earlier initiation of screening and shorter intervals for surveillance [6].Although previous studies have identified CFTR as a tumor suppressor gene that may play a role in early onset of colon cancer [5,7], the pathogenesis of CRC in CF remains unclear. A number of factors can be considered. Thus, stagnant mucus in CF is associated with bacterial overgrowth at the mucosal surface [8,9], which might result in greater levels of tonic microbial stimulation of the epithelia and account for their increased rate of their turnover [10]. It is likely that the altered microbiota composition and microbiota-mucosal interface are also the reasons for a chronic state of low-grade mucosal inflammation in CF [11,12]. Notably, in the colon CFTR is hyper-expressed in the stem cell compartment of the intestinal crypt [13,14], which is the site of CRC origination [15].Than and colleagues have shown altered expression of genes involved in immune cell homeostasis and inflammation, mucins, cell signaling and growth regulation, detoxification and stress response, lipid meta...

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Increased prevalence of colonic adenomas in patients with cystic fibrosis

Abstract: Colonic adenomas are more prevalent in CF patients compared to the general population. This study suggests the need for additional research to support recently published screening guidelines for CF patients.

Cited by 12 publications

References 14 publications

New Comorbidities in the Changing Face of Cystic Fibrosis Care

New Comorbidities in the Changing Face of Cystic Fibrosis Care

Interactions between the gut microbiome and host gene regulation in cystic fibrosis

Interactions between the gut microbiome and host gene regulation in cystic fibrosis

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