Crohn's disease: risk factor for colorectal cancer

Santos, Sandra Cristina Dias dos; Barbosa, Laura Elisabete Ribeiro

doi:10.1016/j.jcol.2016.06.005

Cited by 6 publications

(5 citation statements)

References 43 publications

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“…and Enterobacteriaceae ( Escherichia coli ), which as previously described may contribute to colorectal carcinogenesis [ 63 , 64 , 65 ]. Indeed, several recent studies have shown associations between colorectal cancer and CD activity [ 66 , 67 , 68 ] although a direct cause has not yet been demonstrated. The implication of gut microbiota in the link between CD and cancer would be immense, particularly for microbiota-based therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Microbial Signature in Adipose Tissue of Crohn’s Disease Patients

Serena

Queipo-Ortuño

Millán

et al. 2020

JCM

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Crohn’s disease (CD) is characterized by compromised immune tolerance to the intestinal commensal microbiota, intestinal barrier inflammation, and hyperplasia of creeping fat (CF) and mesenteric adipose tissue (AT), which seems to be directly related to disease activity. Gut microbiota dysbiosis might be a determining factor in CD etiology, manifesting as a low microbial diversity and a high abundance of potentially pathogenic bacteria. We tested the hypothesis that CF is a reservoir of bacteria through 16S-rRNA sequencing of several AT depots of patients with active and inactive disease and controls. We found a microbiome signature within CF and mesenteric AT from patients, but not in subcutaneous fat. We failed to detect bacterial DNA in any fat depot of controls. Proteobacteria was the most abundant phylum in both CF and mesenteric AT, and positively correlated with fecal calprotectin/C-reactive protein. Notably, the clinical status of patients seemed to be related to the microbiome signature, as those with the inactive disease showed a reduction in the abundance of pathogenic bacteria. Predictive functional profiling revealed many metabolic pathways including lipopolysaccharide biosynthesis and sulfur metabolism overrepresented in active CD relative to that in inactive CD. Our findings demonstrate that microbiota dysbiosis associated with CD pathophysiology is reflected in AT and might contribute to disease severity.

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Section: Discussionmentioning

confidence: 99%

Microbial Signature in Adipose Tissue of Crohn’s Disease Patients

Serena

Queipo-Ortuño

Millán

et al. 2020

JCM

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“…It was already known that chronic inflammation creates a microenvironment suitable for the disease progression [33]. dosSantos [34], has identified that a pro-inflammatory state is the cornerstone in the association between CD and CRC, justifying the fact that CD might be a risk factor for CRC. She added that a family history of CRC is an important factor that doubles the risk of CRC in patients with CD.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel pathogenic MSH2 mutation and new DNA repair genes variants: investigation of a Tunisian Lynch syndrome family with discordant twins

et al. 2019

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Background Lynch syndrome (LS) is a highly penetrant inherited cancer predisposition syndrome, characterized by autosomal dominant inheritance and germline mutations in DNA mismatch repair genes. Despite several genetic variations that have been identified in various populations, the penetrance is highly variable and the reasons for this have not been fully elucidated. This study investigates whether, besides pathogenic mutations, environment and low penetrance genetic risk factors may result in phenotype modification in a Tunisian LS family. Patients and methods A Tunisian family with strong colorectal cancer (CRC) history that fulfill the Amsterdam I criteria for the diagnosis of Lynch syndrome was proposed for oncogenetic counseling. The index case was a man, diagnosed at the age of 33 years with CRC. He has a monozygotic twin diagnosed at the age of 35 years with crohn disease. Forty-seven years-old was the onset age of his paternal uncle withCRC. An immunohistochemical (IHC) labeling for the four proteins (MLH1, MSH2, MSH6 and PMS2) of the MisMatchRepair (MMR) system was performed for the index case. A targeted sequencing of MSH2 , MLH1 and a panel of 85 DNA repair genes was performed for the index case and for his unaffected father. Results The IHC results showed a loss of MSH2 but not MLH1, MSH6 and PMS2 proteins expression. Genomic DNA screening, by targeted DNA repair genes sequencing, revealed an MSH2 pathogenic mutation (c.1552C>T; p.Q518X), confirmed by Sanger sequencing. This mutation was suspected to be a causal mutation associated to the loss of MSH2 expression and it was found in first and second degree relatives. The index case has smoking and alcohol consumption habits. Moreover, he harbors extensive genetic variations in other DNA-repair genes not shared with his unaffected father. Conclusion In our investigated Tunisian family, we confirmed the LS by IHC, molecular and in silico investigations. We identified a novel pathogenic mutation described for the first time in Tunisia. These results come enriching the previously reported pathogenic mutations in LS families. Our study brings new arguments to the interpretation of MMR expression pattern and highlights new risk modifiers genes eventually implicated in CRC. Twins discordance reported in this work underscore that disease penetrance could be influenced by both genetic background and environmental factors. Electronic supplementary material The online version of this article (10.1186/s12967-019-1961-9) contains supplementary material, which is available to authorized users.

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“…This can be inferred from the association between chronic inflammatory diseases, such as inflammatory bowel disease and Crohn’s disease, and increased risk for colorectal cancer. 66,67 Obesity is also associated with chronic inflammation, which may play a role in the efficacy of aspirin in preventing colorectal cancer. Rothwell and colleagues recently investigated the effect of aspirin on the risk of cardiovascular events and cancer in a collective of randomized trials and found that the preventative effect of aspirin on cancer risk is dependent upon bodyweight and dose.…”

Section: Introductionmentioning

confidence: 99%

Cancer prevention and screening: the next step in the era of precision medicine

2019

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A primary mode of cancer prevention and early detection in the United States is the widespread practice of screening. Although many strategies for early detection and prevention are available, adverse outcomes, such as overdiagnosis and overtreatment, are prevalent among those utilizing these approaches. Broad use of mammography and prostate cancer screening are key examples illustrating the potential harms stemming from the detection of indolent lesions and the subsequent overtreatment. Furthermore, there are several cancers for which prevention strategies do not currently exist. Clinical and experimental evidence have expanded our understanding of cancer initiation and progression, and have instructed the development of improved, precise modes of cancer prevention and early detection. Recent cancer prevention and early detection innovations have begun moving towards the integration of molecular knowledge and risk stratification profiles to allow for a more accurate representation of at-risk individuals. The future of cancer prevention and early detection efforts should emphasize the incorporation of precision cancer prevention integration where screening and cancer prevention regimens can be matched to one’s risk of cancer due to known genomic and environmental factors.

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Crohn's disease: risk factor for colorectal cancer

Cited by 6 publications

References 43 publications

Microbial Signature in Adipose Tissue of Crohn’s Disease Patients

Microbial Signature in Adipose Tissue of Crohn’s Disease Patients

Identification of novel pathogenic MSH2 mutation and new DNA repair genes variants: investigation of a Tunisian Lynch syndrome family with discordant twins

Cancer prevention and screening: the next step in the era of precision medicine

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