Alimentary Tract
Coeliac disease characteristics, compliance to a gluten free diet and risk of lymphoma by subtype

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Abstract

Objective

Coeliac disease is associated with an increased risk of malignant lymphomas. We investigated the importance of coeliac disease characteristics and diet compliance for risk of lymphoma.

Methods

In a nested case–control design, we identified 59 patients with lymphoma and 137 matched controls from a population-based cohort of 11,650 inpatients with coeliac disease. We assessed coeliac disease characteristics at diagnosis and dietary compliance collected prospectively from medical records during follow-up.

Results

Poor compliance was not significantly associated with risk of lymphoma overall (odds ratio 1.83, 95% confidence interval 0.78–4.31) nor of lymphoma subtypes. Risk estimates differed by subtype; risk of T-cell lymphoma (odds ratio 1.01, confidence interval 0.32–3.15) or intestinal lymphoma (odds ratio 0.66, confidence interval 0.17–2.56) was unelevated, whereas there was an indication of a risk increase of B-cell lymphoma (odds ratio 4.74, confidence interval 0.89–25.3) or extraintestinal lymphoma (odds ratio 3.00, confidence interval 0.73–12.3) following poor compliance. History of weight loss (odds ratio 2.89, confidence interval 1.00–8.29) at coeliac disease diagnosis was associated with an increased risk of lymphoma when excluding tumours occurring with short latency (<3 years).

Conclusions

Compliance to a gluten-free diet did not significantly alter lymphoma risk, but a moderate effect cannot be excluded. Weight loss, a potential marker of coeliac disease severity, may be associated with lymphoma risk.

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

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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.

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