Association of celiac disease and intestinal lymphomas and other cancers

doi:10.1053/j.gastro.2005.02.027

Gastroenterology

Volume 128, Issue 4, Supplement 1, April 2005, Pages S79-S86

https://doi.org/10.1053/j.gastro.2005.02.027 Get rights and content

Celiac disease (CD) is associated with intestinal lymphoma and other forms of cancer, especially adenocarcinoma of the small intestine, of the pharynx, and of the esophagus. Enteropathy-associated T-cell lymphoma (EATL) is a rare form of high-grade, T-cell non-Hodgkin lymphoma (NHL) of the upper small intestine that is specifically associated with CD. This NHL subtype arises in patients with either previously or concomitantly diagnosed CD. In a subgroup of patients, there is progressive deterioration of a refractory form of CD. EATL derives from a clonal proliferation of intraepithelial lymphocytes and is often disseminated at diagnosis. Extraintestinal presentations are not uncommon in the liver/spleen, thyroid, skin, nasal sinus, and brain. The outlook of EATL is poor. Recent studies indicated that (1) CD is associated with a significantly increased risk for NHL, especially of the T-cell type and primarily localized in the gut (EATL); (2) the CD-lymphoma association is less common than previously thought, with a relative risk close to 3; (3) CD screening is not required in patients with NHL of any primary site at the onset, unless suggested by specific findings (T-cell origin and/or primary gut localization). The risk of NHL associated with clinically milder (or silent) forms could be lower than in typical cases of CD. Several follow-up studies suggest that the GFD protects from cancer development, especially if started during the first years of life. Strict adherence to the GFD seems to be the only possibility of preventing a subset of rare but very aggressive forms of cancer.

Section snippets

EATL

EATL is an intestinal T-cell lymphoma that can occur in adults, with a peak in the sixth decade of life. Not a single case of EATL was found in a series of CD-associated tumors in children,¹² indicating that many years of latency need to occur between the onset of CD and the development of EATL. With an annual incidence rate of 0.5–1 per million people in Western countries, this is a rare form of cancer, covering approximately 35% of all small bowel lymphomas. By definition, this NHL subtype

Possible mechanisms of carcinogenesis

The mechanisms responsible for the development of malignancies in patients with CD are not known. The following explanations have been suggested: increased intestinal permeability of environmental carcinogens, chronic inflammation, chronic antigenic stimulation, release of proinflammatory cytokines, immune surveillance problems, and nutritional deficiencies caused by the disease or the GFD.³¹

Given the long latency between CD and cancer development, it seems logical to hypothesize that this is a

The magnitude of the NHL risk

From the public health perspective, the magnitude of NHL risk associated with CD is important, but this was far from clear until recently. Previous studies indicated a strongly increased relative risk (RR), in the range of 40 to 100, emphasizing the high prevalence of this association in adults with CD.7, 10 Such a “pessimistic” point of view was apparently confirmed by mortality analysis in CD patients showing an 11.4- to 69-fold increased risk of dying from lymphoma.5, 34, 35

In recent years,

Does the GFD protect against cancer development?

Conflicting data on the protective effect of treatment with the GFD on the development of malignancy have recently been reviewed.³⁹ It is evident that cancer may arise in subjects who have been treated with the GFD, sometimes for years.³¹ This finding apparently denies any beneficial effect of dietary treatment of CD on cancer risk. However, many of these cases had previously been exposed to dietary gluten for a long time, usually for some decades, whereas the period on GFD was brief.³¹ Thus,

Conclusions

CD is associated with a definite increase in the risk of developing cancer, especially EATL and other gastrointestinal cancers that are partially responsible for the overall increased mortality reported in CD patients. However, the magnitude of the overall risk of NHL is much lower than previously thought, with a relative risk most probably ranging between 2 and 4. There is compelling evidence to suggest that the GFD protects against the development of CD-associated malignancies, especially if

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Association of celiac disease and intestinal lymphomas and other cancers

Section snippets

EATL

Possible mechanisms of carcinogenesis

The magnitude of the NHL risk

Does the GFD protect against cancer development?

Conclusions

Lancet

Gastroenterology

Gastroenterology

Clin Lymphoma

Blood

Lancet

Am J Med

Gastroenterology

Blood

Eur J Cancer

Am J Med

Gastroenterology

Lancet

The clinical and biochemical syndrome in lymphoma and allied diseases involving the mesenteric lymph glands

BMJ

Intestinal reticulosis as a complication of idiopathic steatorrhoea

Gut

Coeliac disease, gluten free diet and malignancy

Gut

Humoral response to wheat protein in patients with coeliac disease and enteropathy associated T cell lymphoma

Br Med J

Increased incidence of malignancy in dermatitis herpetiformis

Br Med J

Risk of lymphoma in patients with dermatitis herpetiformis

Br Med J

Malignancy in celiac disease. Effect of a gluten-free diet

Gut