Cereal Grain Proteins

Some Topics

Gluten & Cancer

A striking association is that celiac disease predisposes patients to the eventual development of lymphoma and other cancers. If this relationship is re-stated as "cereal grains cause cancer," the implication is more easily understood. There is evidence that strict adherence to a gluten-free diet long term will reduce the incidence of lymphoma.

High-grade T-cell lymphomas of the small intestine are the most common neoplasms. The intestinal mucosa distant from the tumor contains T cells often of the same clone as the high-grade T-cell lymphoma. It appears that the T-cell lymphoma evolves from reactive intraepithelial lymphocytes through a low-grade lymphocytic neoplasm to a high-grade tumor.  Ulcers may appear in the jejunum and are probably part of the same disease process, occurring when the neoplastic T-cells are low grade and recognition of tumor cells in biopsies of the ulcers may be impossible. Patients with enteropathy-associated T-cell lymphoma have genetic markers - the HLA DQA1*0501, DQB1*0201 phenotype, although additional HLA-DR/DQ alleles may represent risk factors for lymphoma development. (see abstract)

Carcinoma of the pharynx and esophagus, and adenocarcinoma of the small intestine, are increased in frequency in patients with celiac disease. The increased risk of carcinoma of the esophagus may be related to vitamin A deficiency.

Malignancy and survival in dermatitis herpetiformis: a comparison with coeliac disease.

Author Collin P; Pukkala E; Reunala T
Address Medical School, University of Tampere, Finland.
Source Gut, 1996 Apr, 38:4, 528-30

BACKGROUND--Dermatitis herpetiformis is a lifelong, gluten sensitive skin disease. Patients with dermatitis herpetiformis, similar to patients with coeliac disease not adhering to a gluten free diet, seem to have increased risk for lymphoma. AIMS--This study looked at the occurrence of malignancy and survival of patients with dermatitis herpetiformis and compared the results with those seen in patients with coeliac disease or in the general population. PATIENTS--A total of 305 adult patients with dermatitis herpetiformis diagnosed at the University Hospital of Tampere in 1970-1992 were studied. Most patients started a gluten free diet and at the end of the study 93% of the patients were adhering to the diet. A control group comprised 383 adult patients with coeliac disease, 81% of them adhered to a gluten free diet, 6% had a normal diet, and in 13% the diet history remained unknown. METHODS--The occurrence of malignant diseases and survival of the patients were assessed up to the end of 1993. Standardised incidence ratios (SIR) with 95% confidence intervals were used for the malignant diseases. The survival of the patients was compared with that of the general population. RESULTS--Thirteen (4.3%) patients with dermatitis herpetiformis developed 14 malignant disorders during the follow up (SIR 1.25; 95% confidence intervals 0.68 to 2.09). A non-Hodgkin's lymphoma occurred in four patients with dermatitis herpetiformis, significantly more than expected (SIR 10.3; 2.8-26.3). Thirteen (4.3%) patients with dermatitis herpetiformis died during the follow up but there was no increased general mortality. In coeliac disease, 13 (3.4%) patients developed malignancy (SIR 1.16; 0.62 to 1.97), 31 (8.1%) patients died but the survival rate did not differ from that in the general population. CONCLUSIONS--The incidence of non-Hodgkin's lymphoma was significantly increased in patients with dermatitis herpetiformis. The results also confirm that the patients with dermatitis herpetiformis treated mainly with a gluten free diet have no increased general mortality.

Protective effect of gluten-free diet against development of lymphoma in dermatitis herpetiformis.

Author Lewis HM; Renaula TL; Garioch JJ; Leonard JN; Fry JS; Collin P; Evans D; Fry L
Source Br J Dermatol, 1996 Sep, 135:3, 363-7

Abstract A retrospective study of 487 patients with dermatitis herpetiformis showed that lymphoma developed in eight patients, the expected incidence being 0.21 (standardized registration ratio 3810). All lymphomas occurred in patients whose dermatitis herpetiformis had been controlled without a gluten-free diet (GFD) or in those who had been treated with a GFD for less than 5 years. The results are suggestive of a protective role for a GFD against lymphoma in dermatitis herpetiformis and give further support for advising patients to adhere to a strict GFD for life.

Primary T cell CD30-positive anaplastic large-cell lymphoma associated with adult-onset celiac disease and presenting with skin lesions.

Author Mantovani G; Esu S; Astara G; Lampis B; MacciÄo A; Usai P; Santa Cruz G; Mura E; Ferreli A
Source Acta Haematol, 1995, 94:1, 48-51

We report the case of a 52-year-old woman with primary CD30+ anaplastic large-cell lymphoma of T cell phenotype with skin involvement, stage IVB, fulfilling almost all the clinical, histopathologic and immunophenotypic criteria for this disease, associated with adult-onset celiac disease. The diagnoses of malignancy and celiac disease were made during the same clinical episode. The clinical course of the patient has been extremely favorable and she is in complete remission, 15 months after finishing consolidation therapy.

Study of the immunohistochemistry and T cell clonality of enteropathy-associated T cell lymphoma.

Author Murray A; Cuevas EC; Jones DB; Wright DH
Source Am J Pathol, 1995 Feb, 146:2, 509-19

Specimens from 23 patients with enteropathy-associated T cell lymphoma were studied by immunohistochemistry after antigen retrieval. Specimens from 14 of these patients were investigated for the presence of clonal T cell gene rearrangements in both the tumor and the adjacent enteropathic intestine by the polymerase chain reaction. Primers for T cell receptor beta and gamma genes were used in a combination that permits the identification of approximately 90% of T cell receptor rearrangements. Clonal rearrangements of the T cell receptor were found in 13 of the 14 tumors studied. Specimens of enteropathic bowel resected with the tumor, but showing no morphological or immunohistochemical evidence of tumor involvement, showed clonal T cell receptor gene rearrangements in 11 cases. In 10 of these, the amplified DNA was of the same molecular weight in the enteropathic bowel as in the corresponding tumor. In 2 cases, sequencing the polymerase chain reaction product showed identical T cell receptor gene rearrangements in the tumor and in the adjacent intestine. Uniform staining for p53 was seen in 22 of the 23 tumors. In 9 of 19 cases studied, collections of small lymphocytes in the enteropathic bowel expressed p53. In all but one of these specimens, a clonal rearrangement of the T cell receptor genes was identified. We interpret these findings as support for the concept that enteropathy-associated T cell lymphoma arises on a background of gluten-sensitive enteropathy with evolution of neoplastic T cell clones from the reactive T cell population present in the enteropathic bowel.

Enteropathy-associated T-cell lymphoma in the West of Ireland: low-frequency of Epstein-Barr virus in these tumors.

Author Walsh SV; Egan LJ; Connolly CE; Stevens FM; Egan EL; McCarthy CF
Source Mod Pathol, 1995 Sep, 8:7, 753-7

Abstract The Epstein-Barr virus has been implicated in the etiology of endemic Burkitt's lymphoma, post-transplant lymphoma, large-cell anaplastic CD30 (Ki-1)-positive lymphoma, and in many T-cell lymphomas. A recent report has found Epstein-Barr virus genome in association with 4 of 11 cases (36%) of enteropathy-associated T-cell lymphoma. In a retrospective study, we have characterized 22 consecutive cases of enteropathy-associated T-cell lymphoma from the West of Ireland where celiac disease is endemic. All cases were immunophenotyped with T- and B-cell markers

Premalignant conditions of the small intestine.

Author Ryan JC  Source Semin Gastrointest Dis, 1996 Apr, 7:2, 88-93

Abstract Cancer of the small intestine is rare compared with other sites in the gastrointestinal tract. Of the four major primary small-bowel tumors (adenocarcinomas, lymphomas, carcinoid, and leiomyosarcomas), adenocarcinomas and lymphomas are associated with diseases that seem to increase the risk of developing these malignancies. In the case of immunoproliferative small intestinal disease and celiac disease, both of which are thought to predispose patients to the development of primary lymphoma, treatment of the predisposing conditions seems to decrease the risk of developing subsequent malignancy. Recognition of the increased risk associated with other conditions, such as immunodeficiency syndromes, nodular lymphoid hyperplasia, Crohn's disease, the gastrointestinal polyposis syndromes, hereditary nonpolyposis colon cancer, neurofibromatosis, long-standing ileostomy, and urinary diversion procedures, may lead to early diagnosis and improved survival.

The gut as a lymphoepithelial organ: the role of intestinal epithelial cells in mucosal immunity.

Author Tlaskalova-Hogenova H; Farre-Castany MA; Stepankova R; Kozakova H; Tuckova L; Funda DP; Barot R; Cukrowska B; Sinkora J; Mandel; L; et al Source Folia Microbiol (Praha), 1995, 40:4, 385-91

 Abstract Mucosal surfaces covered by a layer of epithelial cells represent the largest and most critical interface between the organism and its environment. The barrier function of mucosal surfaces is performed by the epithelial layer and immune cells present in the mucosal compartment. As recently found, epithelial cells, apart from their participation in absorptive, digestive and secretory processes perform more than a passive barrier function and are directly involved in immune processes. Besides the well known role of epithelial cells in the transfer of polymeric immunoglobulins produced by lamina propria B lymphocytes to the luminal content of mucosals (secretory Igs), these cells were found to perform various other immunological functions, to interact with other cells of the immune system and to induce an efficient inflammatory response to microbial invasion: enzymic processing of dietary antigens, expression of class I and II MHC antigens, presentation of antigens to lymphocytes, expression of adhesive molecules mediating interaction with intraepithelial lymphocytes and components of extracellular matrix, production of cytokines and probable participation in extrathymic T cell development of intraepithelial lymphocytes. All these functions were suggested to influence substantially the mucosal immune system and its response. Under immunopathological conditions, e.g. during infections and inflammatory bowel and celiac diseases, both epithelial cells and intraepithelial lymphocytes participate substantially in inflammatory reactions. Moreover, enterocytes could become a target of mucosal immune factors. Mucosal immunosurveillance function is of crucial importance in various pathological conditions but especially in the case of the most frequent malignity occurring in the intestinal compartment, i.e. colorectal carcinoma. Proper understanding of the differentiation processes and functions of epithelial cells in interaction with other components of the mucosal immune system is therefore highly desirable.

  • The book, Gluten Problems and Solutions provides both an introduction and also advanced explanations of the immunological basis of gluten induced diseases. The Alpha Nutrition Program is designed to solve the heath problems related to gluten which we consider to be both common and serious. The author is Stephen Gislason MD.

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    Gluten Free: The exclusion of wheat, rye, barley are the initial steps when gluten allergy is suspected. Gluten elimination should be part of a more comprehensive diet revision plan, preferably in the form outlined in the Alpha Nutrition Program. The Program is gluten-free and is recommended as the best diet revision strategy for anyone with diagnosed celiac disease, or any person with symptoms suggestive of gluten allergy. Learn more about the Alpha Nutrition Program. Gluten free recipes are found in the book, Cooking and Recipes.

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