Risk of Colorectal High-Grade Dysplasia and Cancer in a Prospective Observational Cohort of Patients With Inflammatory Bowel Disease

Beaugerie, Laurent; Svrcek, Magali; Seksik, Philippe; Bouvier, Anne–Marie; Simon, Tabassome; Allez, Matthieu; Brixi, Hédia; Gornet, Jean–Marc; Altwegg, Romain; Beau, Philippe; Duclos, Bernard; Bourreille, Arnaud; Faivre, Jean; Peyrin–Biroulet, Laurent; Fléjou, Jean‐François; Carrat, Fabrice

doi:10.1053/j.gastro.2013.03.044

Cited by 309 publications

(205 citation statements)

References 39 publications

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“…One major risk factor of colorectal cancer is inflammatory bowel diseases such as ulcerative colitis (2), indicating that the pathogenesis of colorectal cancer is closely associated with inflammatory responses in the colon, and that manipulation of inflammation might prevent colorectal cancer development. In fact, it is well known that the use of aspirin or other NSAIDs is associated with reduction of risk of colorectal cancer (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…However, extensive use of these drugs is precluded due to their adverse effects such as gastrointestinal toxicity and tendency to cardiovascular accidents (7,8), making essential development of an alternative drug for aspirin. PGs consist of PGD 2 , PGE 2 , PGF 2a , PGI 2 , and thromboxane (TX) A 2 , which are formed from arachidonic acid by sequential actions of COX and respective synthases (6). Because PGE 2 is the most abundant PG found in colorectal cancer (9), numerous studies have been done to analyze actions of this PG in colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

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Definition of Prostaglandin E2–EP2 Signals in the Colon Tumor Microenvironment That Amplify Inflammation and Tumor Growth

et al. 2015

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Inflammation in the colon contributes significantly to colorectal cancer development. While aspirin reduces the colorectal cancer risk, its action mechanism, especially in inflammation in tumor microenvironment, still remains obscure. Here, we examined this issue by subjecting mice deficient in each prostaglandin (PG) receptor to colitis-associated cancer model. Deficiency of PGE receptor subtype EP2 selectively reduced, and deficiency of EP1 and EP3 enhanced, the tumor formation. EP2 is expressed in infiltrating neutrophils and tumor-associated fibroblasts in stroma, where it regulates expression of inflammation-and growth-related genes in a self-amplification manner. Notably, expression of cytokines such as TNFa and IL6, a chemokine, CXCL1, a PG-producing enzyme, COX-2, and Wnt5A was significantly elevated in tumor lesions of wild-type mice but this elevation was significantly suppressed in EP2-deficient mice. Intriguingly, EP2 stimulation in cultured neutrophils amplified expression of TNFa, IL6, CXCL1, COX-2, and other proinflammatory genes synergistically with TNFa, and EP2 stimulation in cultured fibroblasts induced expression of EP2 itself, COX-2, IL6, and Wnt genes. EP2 expression in infiltrating neutrophils and tumor-associated fibroblasts was also found in clinical specimen of ulcerative colitis-associated colorectal cancer. Bone marrow transfer experiments suggest that EP2 in both cell populations is critical for tumorigenesis. Finally, administration of a selective EP2 antagonist potently suppressed tumorigenesis in this model. Our study has thus revealed that EP2 in neutrophils and tumor-associated fibroblasts promotes colon tumorigenesis by amplifying inflammation and shaping tumor microenvironment, and suggests that EP2 antagonists are promising candidates of aspirin-alternative for chemoprevention of colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Definition of Prostaglandin E2–EP2 Signals in the Colon Tumor Microenvironment That Amplify Inflammation and Tumor Growth

et al. 2015

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“…This connection is particularly evident in colon carcinogenesis, because patients with inflammatory bowel disease (IBD) have as much as 7-fold higher incidence of colon cancer than the general population (3). Also, the use of NSAIDs reduces the risk of colon cancer in patients with familial adenomatous polyposis coli and patients with sporadic adenomas (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs

Degagné¹,

Pandurangan²,

Bandhuvula³

et al. 2014

J. Clin. Invest.

137

139

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“…Estudios han mostrado que pacientes con EII tienen mayor riesgo de desarrollar CCR, con una prevalencia de 3,7% para CU y un riesgo relativo global de 2,5 para EC 7,20 . Sin embargo, estudios recientes señalan una frecuencia de CCR menor a la descrita previamente 21 . La historia familiar de CCR, menor edad al diagnóstico de EII, extensión y duración de la enfermedad, severidad de la inflamación y la presencia de CEP han sido señalados como factores de riesgo de CCR 2 .…”

Section: Discussionunclassified

Desarrollo de neoplasia en pacientes con enfermedad inflamatoria intestinal

et al. 2015

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Risk of Colorectal High-Grade Dysplasia and Cancer in a Prospective Observational Cohort of Patients With Inflammatory Bowel Disease

Cited by 309 publications

References 39 publications

Definition of Prostaglandin E2–EP2 Signals in the Colon Tumor Microenvironment That Amplify Inflammation and Tumor Growth

Definition of Prostaglandin E2–EP2 Signals in the Colon Tumor Microenvironment That Amplify Inflammation and Tumor Growth

Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs

Desarrollo de neoplasia en pacientes con enfermedad inflamatoria intestinal

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