People with coeliac disease are at a modestly increased risk of malignancy and mortality than the general population. The risks were most apparent in the year after diagnosis, and the decreased risks thereafter suggest that some of the overall excess risk was likely to be due to ascertainment. Although people with coeliac disease had an increased risk of gastrointestinal and lymphoproliferative malignancy compared with the general population they had around one third the risk of breast or lung cancer.
A potential weakness of epidemiological studies using routinely collected data such as that in the general practice research database is the validity of diagnostic data for each person, particularly histological status; the diagnosis of coeliac disease has not been specifically validated in the database. One study looked in detail at the accuracy of the diagnosis of inflammatory bowel disease (92%) and one similarly evaluated cancer diagnoses (> 90%).11-14
Furthermore, to increase the specificity of the diagnosis, we restricted our analyses to people with coeliac disease who had at least one prescription for a gluten-free product. In these analyses there were no substantial changes in the effect estimates.
The likelihood of detecting an occult or overt malignancy may be increased during the investigation of coeliac disease and conversely coeliac disease is more likely to be detected during the investigation of cancer. The excess risk of gastrointestinal malignancy is therefore likely to be attributable to the more detailed investigation of gastrointestinal symptoms, particularly at presentation. We were able to assess the effect of potential confounders such as body mass index and smoking status on risk of malignancy and mortality. We found no evidence of confounding despite incomplete data and the likely heterogeneous nature of those people with missing data.
The risks of overall malignancy and mortality in people with coeliac disease suggest more modest increases than in other studies. The most recent study found slightly greater risks of malignancy (standardised incidence ratio 1.3) and mortality (standardised mortality ratio 2.0) compared with our study.7,8
These greater risks may reflect more severe disease at presentation or a period effect, as all the patients had been admitted to hospital at least once and follow up ended at least six years earlier than in our study. People being diagnosed more recently seem to have less severe disease.15-18
Most other studies have found increased risks of twofold or more for malignancy or mortality.1,2,4,5
Two previous studies have also suggested a decreased risk of breast cancer among women with coeliac disease, but it is not clear whether these were chance observations.4,8
It seems unlikely that socioeconomic status is an important confounder in this relation as breast cancer has been consistently associated with higher socioeconomic groups, and there is no evidence that people with coeliac disease are of lower socioeconomic status.19
The reduction in incidence of lung cancer found by us is in keeping with recent studies, which showed that people with coeliac disease report smoking less even before they were diagnosed as having the disease.20,21
That the reduced incidence is still apparent after adjusting for smoking status is surprising, but our data on smoking were incomplete so residual confounding remains a possibility.
Most of the modest increases in the relative and absolute risk of malignancy and mortality in people with coeliac disease occurs in the year after diagnosis, and although there are noticeably increased risks of some malignancies such as gastrointestinal cancers and lymphoma there are substantial reductions in the risk of other, common, cancers such as those of the lung and breast. The findings for lung and breast cancer are of interest because of possible genetic, nutritional, or environmental factors that may protect people with coeliac disease against certain malignancies. By understanding the mechanism of protection in people with coeliac disease we may gain insight into the causes of breast cancer.
What is already known on this topic
People with coeliac disease may be at increased risk of gastrointestinal malignancy and lymphoma
These risks have not been quantified in contemporary, population based studies
What this study adds
People with coeliac disease have a modestly increased risk of malignancy and mortality
Most of the excess risk occurs in the year after diagnosis
The risk of breast cancer is about a third that of the general population
The risk of lung cancer is about a third that of the general population, probably because people with coeliac disease smoke less