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.
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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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DOI: https://doi.org/10.1007/s10552-011-9818-4