Alimentary TractCoeliac disease characteristics, compliance to a gluten free diet and risk of lymphoma by subtype☆
Introduction
Coeliac disease (CD) is one of the most common chronic autoimmune disorders worldwide with a prevalence of 1% in western populations [1]. CD is characterized by small intestinal mucosal lesions, secondary to a T-cell-mediated inflammatory response triggered by gluten exposure [2] and is associated with a 3- to 6-fold increased risk of malignant lymphoma overall [3], [4], [5], [6], [7], [8]. It has consistently been reported that the relative risk of intestinal or T-cell lymphoma is higher than extraintestinal or B-cell lymphoma in CD patients [3], [4], [5], [6], [7].
It is unclear whether the increased risk of lymphoma pertains equally to individuals with different phenotypes of CD or to individuals that respond differently to a gluten-free diet (GFD) [9], [10]. Only a few studies have directly evaluated the role of dietary compliance in lymphoma development [6], [11], [12]. These previous reports were, however, limited by small sample size (n = 9, 9 and 10, respectively) and did not formally compare groups of patients with different degrees of dietary compliance, nor examined the potential effect of a GFD by specific subtypes of lymphoma.
With the aim to identify potential predictors of lymphoma in CD, we performed a detailed case–control study nested within a population-based cohort of hospitalized CD patients, using prospectively recorded medical file exposure data.
Section snippets
Underlying CD cohort
This case–control study was nested in a previously identified cohort of individuals (n = 11,650) with a hospital discharge diagnosis of CD (1964–1995) in the Swedish Hospital Discharge Register [4], [13]. In this CD cohort, 73% of the patients were hospitalized with CD as children or adolescents (median age at diagnosis of CD was 2 years in the underlying cohort of CD patients in which this study was nested) and 10% were in their sixties or older. The majority were diagnosed between 1984 and 1995
Results
The majority of the study participants were female. The median age at diagnosis of CD was 61 years (Table 1) in cases and controls. Most patients were diagnosed with CD before 1990, when serological screening was unavailable. The median latency time between the diagnoses of CD and lymphoma was 34 months (Table 1).
Discussion
In this nested case–control study using rigorously collected prospective data on CD characteristics and diet compliance, we did not find a statistically significantly increased risk of lymphoma overall in individuals with poor dietary compliance. However, there were indications of heterogeneity in risk by NHL subtype as risk estimates were several-fold elevated for B-cell and extraintestinal lymphoma, but non-elevated for T-cell and intestinal lymphoma in patients diagnosed with CD as adults.
Conflict of interest
None declared.
Ethical approval
This project (99-299) was approved by the Regional Ethics Review Board in Stockholm, Sweden on the 7th February 2000.
Acknowledgements
OO was supported by grants from Stiftelsen Samariten, Sachs’ Children's Hospital, Stockholm South General Hospital and the Department of Clinical Science and Education, Karolinska Institute, Sweden whilst writing this article.
This project was also supported by a grant from the Swedish Society of Medicine, the Swedish Research Council, the Karolinska Institutet, the Majblomman Foundation, the Juhlin Foundation, the Clas Groschinsky Foundation and the Swedish Coeliac Society.
Independence (role of
References (34)
- et al.
The prevalence of celiac disease in average-risk and at-risk Western European populations: a systematic review
Gastroenterology
(2005) - et al.
Cancer incidence in a population-based cohort of individuals hospitalized with celiac disease or dermatitis herpetiformis
Gastroenterology
(2002) - et al.
Increased risk for non-Hodgkin lymphoma in individuals with celiac disease and a potential familial association
Gastroenterology
(2009) - et al.
Hematologic manifestations of celiac disease
Blood
(2007) - et al.
Risk of malignancy in patients with celiac disease
Am J Med
(2003) - et al.
A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease
Am J Clin Nutr
(2007) - et al.
Safe gluten threshold for patients with celiac disease: some patients are more tolerant than others
Am J Clin Nutr
(2007) - et al.
Mortality in patients with coeliac disease and their relatives: a cohort study
Lancet
(2001) - et al.
Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma. French Coeliac Disease Study Group
Lancet
(2000) - et al.
Non-Hodgkin lymphoma
Lancet
(2003)
The epidemiology of non-Hodgkin lymphoma
Pathology
Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium
Blood
Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma
Clin Gastroenterol Hepatol
Coeliac disease: dissecting a complex inflammatory disorder
Nat Rev Immunol
Risk of non-Hodgkin lymphoma in celiac disease
JAMA
Malignancy and mortality in people with coeliac disease: population based cohort study
BMJ (clinical research ed.)
Effect of a gluten-free diet on the risk of enteropathy-associated T-cell lymphoma in celiac disease
Dig Dis Sci
Cited by (44)
Celiac disease
2023, Revue de Medecine InterneImmune-mediated enteropathies: From bench to bedside
2021, Journal of AutoimmunityGluten-related disorders: Monitoring and follow-up
2021, Gluten-Related Disorders: Diagnostic Approaches, Treatment Pathways, and Future PerspectivesNutrition Assessment, Interventions, and Monitoring for Patients with Celiac Disease: An Evidence Analysis Center Scoping Review
2020, Journal of the Academy of Nutrition and DieteticsCitation Excerpt :These studies assessed various outcomes, including adherence/management,35,38 gastrointestinal symptoms and conditions,35,36 immunology/serology measures,35,39 mental/cognitive health,35,37 and quality of life (Figure 4).35,37,39 Eight systematic review/meta-analysis,42-49 9 experimental trials,50-58 and 176 observational studies59-234 examined the effects of gluten-free diet. Most of the systematic reviews/meta-analyses44-49 were published between 201544,45 and 2018.48,49
Celiac disease and non-celiac gluten or wheat sensitivity and health in later life: A review
2018, MaturitasCitation Excerpt :In addition, the impact that adherence to the GFD may have on malignancies’ risk remains contradictory. A high lymphoma risk has been found independently of adherence to GFD [13,19], while Elfstrom et al. [18] comment that the reduction noted post-diagnostically could be hardly attributed to GFD initiation, as the same pattern of cancer incidence was found in individuals with inflammation but no villus atrophy, who do not follow GFD. On the contrary, an impressive decrease in the risk for gastrointestinal cancers and NHL was seen in patients with CD [20] or dermatitis herpetiformis (DH) [21], so that the excess morbidity rate did not differ from that of the general population for those patients strictly adhering to GFD for more than five years.
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Ola Olén had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.