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Non-Hodgkin lymphoma and gluten-sensitive enteropathy: estimate of risk using meta-analyses

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Abstract

Objectives

Gluten-sensitive enteropathy, including coeliac disease and dermatitis herpetiformis, is associated with non-Hodgkin lymphoma (NHL), and particularly enteropathy-associated T-cell lymphoma (EATCL). We conducted a meta-analysis to quantify the association.

Methods

Fifty-four risk estimates (range 0.28–300) were pooled using random-effects meta-analysis. Potential sources of variation were examined using sensitivity analyses and meta-regression.

Results

Thirty-one estimates with gluten-sensitive enteropathy diagnosed by serology then biopsy, serology alone, or recorded in medical notes accounted for half the variation in risks, giving a pooled estimate of 4.42 (95% confidence interval (CI) 3.72–5.26, I 2 = 0%). Men and women had similar pooled risks. Risks were largest when these conditions were diagnosed using biopsy and lowest when self-reported. Study design, comparison population, geography or gluten-sensitive enteropathy type explained less of the variation. EATCL estimates ranged from 6 to 200; an association with diffuse large B-cell lymphoma (DLBCL) was also observed (pooled risk estimate = 1.97, 95% CI 1.23–3.15).

Conclusions

Where gluten-sensitive enteropathy was diagnosed using modern techniques, NHL risk was increased fourfold. At this level, one in 2,000 persons with gluten-sensitive enteropathy develops NHL each year. In addition to EATCL, DLBCL and possibly other subtypes may be linked to these conditions, and these weaker associations could be investigated in large population-based cohorts with biological samples.

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Abbreviations

AgA:

Antigliadin antibodies

CI:

Confidence interval

DH:

Dermatitis herpetiformis

DLBCL:

Diffuse large B-cell lymphoma

EMA:

Endomysial antibodies

EATCL:

Enteropathy-associated T-cell lymphoma

IgA:

Immunoglobulin antibodies

NHL:

Non-Hodgkin lymphoma

PI:

Predictive interval

RCD:

Refractory coeliac disease

tTGA:

Tissue transglutaminase antibodies

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Acknowledgments

This work was funded by Leukaemia and Lymphoma Research, UK.

Conflict of interest

There are no conflicts of interest.

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Authors and Affiliations

  1. Epidemiology and Genetics Unit, Department of Health Sciences, University of York, Seebohm Rowntree Building, Heslington, York, YO10 5DD, UK

    Eleanor V. Kane, Rob Newton & Eve Roman

  2. Hull York Medical School, University of York, York, UK

    Rob Newton & Eve Roman

Authors
  1. Eleanor V. Kane
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  2. Rob Newton
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Correspondence to Eleanor V. Kane.

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Supplementary material 1 (DOC 222 kb)

10552_2011_9818_MOESM2_ESM.tif

Supplementary Figure 1: Funnel plot of standard errors of log risk estimate versus risk estimates in studies of non-Hodgkin lymphoma and gluten-sensitive enteropathy. Pooled risk estimate and pseudo 95% confidence limits are from the 31 studies with homogeneous risk estimates. (TIFF 1579 kb)

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Kane, E.V., Newton, R. & Roman, E. Non-Hodgkin lymphoma and gluten-sensitive enteropathy: estimate of risk using meta-analyses. Cancer Causes Control 22, 1435–1444 (2011). https://doi.org/10.1007/s10552-011-9818-4

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