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Background: Coeliac disease has been associated with an increased risk of mortality and malignancy. However, the strength of this association is conflicting among different studies., Aim: To perform a systematic review and quantitative meta-analysis to determine the risk of all-cause mortality, any malignancy and lymphoid malignancy in coeliac disease patients., Methods: Four electronic databases (Medline, PubMed, Embase and Current Contents Connect) were searched to 4 January 2012, with no language restrictions. From 8698 citations identified, a total of 17 studies met our inclusion criteria., Results: The all-cause mortality meta-analysis showed an increased risk for all-cause mortality in coeliac patients [odds ratio (OR) 1.24; 95% confidence interval (CI) 1.19-1.30]. A subgroup analysis showed that patients identified by positive serology alone were also at an increased risk of all-cause mortality (OR 1.16; 95% CI 1.02-1.31). The non-Hodgkin lymphoma (NHL) meta-analysis showed an increased risk for NHL in coeliac patients (OR 2.61; 95% CI 2.04-3.33). A subgroup analysis showed that patients identified by positive serology alone were also at an increased risk of NHL (OR 2.55; 95% CI 1.02-6.36). The T-cell non-Hodgkin lymphoma (TNHL) meta-analysis showed an increased risk of TNHL (OR 15.84; 95% CI 7.85-31.94). The any malignancy meta-analysis showed no increased risk (OR 1.07; 95% CI 0.89-1.29)., Conclusions: Patients with coeliac disease are at an increased risk of mortality and non-Hodgkin lymphoma, particularly T-cell non-Hodgkin lymphoma; they do not have an increased risk of any malignancy overall. Serologically defined patients with coeliac disease have an elevated risk of mortality and non-Hodgkin lymphoma., (© 2012 Blackwell Publishing Ltd.)

The authors offer a response to a commentary by J. F. Ludvigsson about their article "Meta-analysis: coeliac disease and the risk of all-cause mortality, any malignancy and lymphoid malignancy," in the 2012 issue. They agree that a specific diagnosed vs. undiagnosed analysis should have been included in addition to serology vs. non-serology analysis. They also discuss their decision to exclude external comparison in their study to obtain reliable result and avoid overestimation of actual risk.