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European multicentre study on Coeliac disease and non-Hodgkin lymphoma

Objectif



Coeliac disease (CD) is a permanent intolerance for proteins of grains (wheat, rye, barley and possibly oats) called gluten, characterized by villous atrophy of the small intestine. The disease is treated with a gluten-free diet. The incidence of diagnosed CD in Europe is about 1: 2000 live births. Typical cases manifest with chronic diarrhoea, weight loss and abdominaldis tension. However, the clinical spectrum of CD is highly heterogeneous and many CD cases present with extra intestinal complaints, such as anaemia, short stature, pubertal delay, osteoporosis or neurological disorders. Sometimes CD is clinically silent. The widespread use of CD screening tests (determination in serum of IgA antigliadin and anti endomysium antibodies) has shown that, in most European countries, the number of CD cases which remain undiagnosed and untreated is, much higher than the number of patients who are correctly diagnosed on clinical ground. A recent Italian multi centre survey on 17,201apparently healthy students showed a prevalence of CD of 1 in 184 subjects, with a ratio of 1:7 recognized versus unrecognised CD cases. These results indicate that in Europe CD is one of the most common lifelong disorders. Persons with CD have malignancies, especially of the gastrointestinal tract, at a significantly higher frequency than the general population: 8.1-13.3% of the patients develop cancer. In CD there is a 43-fold relative risk (RR) for non-Hodgkin small bowel Iymphoma, a 12-fold RR for oesophagus cancer and a10-fold RR for cancer of the mouth and pharynx. A prolonged treatment with a gluten-free diet seems to play a protective role against cancer in these patients. Recent studies suggest that patients with untreated CD are also at high risk of developing non-Hodgkin Iymphoma (NHL) of any primary site. Patients affected by dermatitis herpetiform is, which is considered one of the many clinical forms of CD, are at 5-10 fold risk of developing NHL. While primary intestinal Iymphoma is a rare condition; NHL is one of the most commonneo plastic disorders in Europe. The purpose of this study is to evaluate whether in Europe untreated CD is a primary risk factor to developed NHL at anyprimary site and to quantify the relative risk. The hypothesis is that in Europe untreated (unrecognised. subclinical a symptomatic. neglected) CD is responsible for a heavy burden of preventable malignancies in the general European population. Plan of investigation: Multicentre, European, prospective, case-control study. Cases: persons with NHL at onset identified in defined areas. Controls: patients sex and age-matched to the cases, seen at hospitals for disorders not related to CD. The existence of untreated CD will be investigated in cases and in controls by means of clinical, serological, histological and HLA studies. The hypothesis will be indirectly tested by comparing the prevalence of CD in subjects with NHL and in the controls. Relevance: This study represents a significant step forward on the epidemiological European research to determinate abnormalities which can predispose to cancer. If the prevalence for NHL is significantly increased in untreated CD the identification and treatment of missed cases of CD should become important in the prevention of cancer in Europe and in the improvement of the health of the European population.

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Academisch Ziekenhuis Leiden
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Adresse
2,Albinusdreef
2333 ZA Leiden
Pays-Bas

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