Association Between Celiac Disease and Cancer

Marafini, Irene; Monteleone, Giovanni; Stolfi, Carmine

doi:10.3390/ijms21114155

Cited by 49 publications

(31 citation statements)

References 86 publications

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“…However, in a small fraction of patients, the symptoms/signs of malabsorption and villous atrophy can persist or recur despite a strict gluten-free diet. This condition is termed refractory celiac disease (RCD) and associates with an elevated risk of complications [ 58 , 59 ]. The pathogenesis of RCD is not fully understood but many inflammatory cytokines produced in the inflamed gut of these patients are supposed to amplify the tissue-destructive immune response [ 60 ].…”

Section: Smad7 In Other Inflammatory Pathologies Of the Gutmentioning

confidence: 99%

Involvement of Smad7 in Inflammatory Diseases of the Gut and Colon Cancer

Troncone

Marafini

Stolfi

et al. 2021

IJMS

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In physiological conditions, the human intestinal mucosa is massively infiltrated with various subsets of immune cells, the activity of which is tightly regulated by several counter-regulatory factors. One of these factors is transforming growth factor-β1 (TGF-β1), a cytokine produced by multiple cell types and targeting virtually all the intestinal mucosal cells. Binding of TGF-β1 to its receptors triggers Smad2/3 signaling, thus culminating in the attenuation/suppression of immune–inflammatory responses. In patients with Crohn’s disease and patients with ulcerative colitis, the major human inflammatory bowel diseases (IBD), and in mice with IBD-like colitis, there is defective TGF-β1/Smad signaling due to high levels of the intracellular inhibitor Smad7. Pharmacological inhibition of Smad7 restores TGF-β1 function, thereby reducing inflammatory pathways in patients with IBD and colitic mice. On the other hand, transgenic over-expression of Smad7 in T cells exacerbates colitis in various mouse models of IBD. Smad7 is also over-expressed in other inflammatory disorders of the gut, such as refractory celiac disease, necrotizing enterocolitis and cytomegalovirus-induced colitis, even though evidence is still scarce and mainly descriptive. Furthermore, Smad7 has been involved in colon carcinogenesis through complex and heterogeneous mechanisms, and Smad7 polymorphisms could influence cancer prognosis. In this article, we review the data about the expression and role of Smad7 in intestinal inflammation and cancer.

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Section: Smad7 In Other Inflammatory Pathologies Of the Gutmentioning

confidence: 99%

Involvement of Smad7 in Inflammatory Diseases of the Gut and Colon Cancer

Troncone

Marafini

Stolfi

et al. 2021

IJMS

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“…In addition, the presence of autoimmune diseases is now recognized as a risk factor of some types of cancer. For example, celiac disease, a systemic autoimmune disorder associated with chronic inflammation, is associated with the occurrence of gastric cancer and intestinal lymphomas in distinct cohorts of individuals ( 116 ).…”

Section: Inflammation and Cancermentioning

confidence: 99%

Old and New Players of Inflammation and Their Relationship With Cancer Development

et al. 2021

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Pathogens or genotoxic agents continuously affect the human body. Acute inflammatory reaction induced by a non-sterile or sterile environment is triggered for the efficient elimination of insults that caused the damage. According to the insult, pathogen-associated molecular patterns, damage-associated molecular patterns, and homeostasis-altering molecular processes are released to facilitate the arrival of tissue resident and circulating cells to the injured zone to promote harmful agent elimination and tissue regeneration. However, when inflammation is maintained, a chronic phenomenon is induced, in which phagocytic cells release toxic molecules damaging the harmful agent and the surrounding healthy tissues, thereby inducing DNA lesions. In this regard, chronic inflammation has been recognized as a risk factor of cancer development by increasing the genomic instability of transformed cells and by creating an environment containing proliferation signals. Based on the cancer immunoediting concept, a rigorous and regulated inflammation process triggers participation of innate and adaptive immune responses for efficient elimination of transformed cells. When immune response does not eliminate all transformed cells, an equilibrium phase is induced. Therefore, excessive inflammation amplifies local damage caused by the continuous arrival of inflammatory/immune cells. To regulate the overstimulation of inflammatory/immune cells, a network of mechanisms that inhibit or block the cell overactivity must be activated. Transformed cells may take advantage of this process to proliferate and gradually grow until they become preponderant over the immune cells, preserving, increasing, or creating a microenvironment to evade the host immune response. In this microenvironment, tumor cells resist the attack of the effector immune cells or instruct them to sustain tumor growth and development until its clinical consequences. With tumor development, evolving, complex, and overlapping microenvironments are arising. Therefore, a deeper knowledge of cytokine, immune, and tumor cell interactions and their role in the intricated process will impact the combination of current or forthcoming therapies.

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“…EATL is a rare tumor with a slightly higher male predominance and presents at a median age of 60. EATL is peripheral or extranodal T-cell lymphoma arising in the small intestine and is commonly associated with CD [ 1 ]. It accounts for 4.2% of all peripheral T-cell lymphomas, which is more common in Europeans due to the increased incidence of celiac disease [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

Hematemesis as an Initial Presentation of Enteropathy-Associated T-Cell Lymphoma

Bassi¹,

Mohapatra²,

Sharma³

et al. 2021

Cureus

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Enteropathy-associated T-cell lymphoma (EATL) is a tumor of intraepithelial T-lymphocytes arising in the small intestine. Based on the genetic profile, immunohistochemistry, and histology, EATL is divided into two subtypes. EATL type I occurs in individuals with celiac disease (CD) while EATL type II is a sporadic form that occurs in individuals without CD. Intensive chemotherapy and surgery are the mainstay treatment. However, despite the currently available treatment options, the five-year survival rate is only 9%. EATL presents as abdominal pain, nausea, or slow gastrointestinal bleeding. Severe bleeding leading to hemodynamic instability is rarely known in EATL. Therefore, we present a unique case of EATL who presented with acute and severe gastrointestinal bleeding with no prior history of CD.

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Association Between Celiac Disease and Cancer

Cited by 49 publications

References 86 publications

Involvement of Smad7 in Inflammatory Diseases of the Gut and Colon Cancer

Involvement of Smad7 in Inflammatory Diseases of the Gut and Colon Cancer

Old and New Players of Inflammation and Their Relationship With Cancer Development

Hematemesis as an Initial Presentation of Enteropathy-Associated T-Cell Lymphoma

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