Letter: gastric cancer and pernicious anaemia - often Helicobacter pylori in disguise; authors' reply



We thank Rugge et al. for the interesting comments on our systematic review on the incidence of gastric cancer (GC) in pernicious anaemia (PA).[1] The meta-analysis showed an overall GC relative risk in PA of 6.8.[2] This figure is the result of a rigorous selection of the published literature on this item, i.e. GC and PA, without any time restriction, including finally in the meta-analysis only six papers published from 1977 to 2010 from the initially identified 27 articles which met eligibility criteria.

As stated in the discussion, in this systematic review, unfortunately the type of gastritis underlying the diagnosis of PA could not be evaluated because these data were not systematically described in the included studies. The diagnosis of PA was mainly made by blood tests, Schilling test or bone marrow evaluation and only in two studies by histology of fundic biopsies.

Analogously, it was not possible to take account of Helicobacter pylori as a possible aetiological factor of the autoimmune gastritis associated with PA as well as known risk factor for GC, because about half of the included studies precede the discovery of H. pylori. Some studies reported that H. pylori infection is an infrequent finding in PA patients, suggesting that the pathological process in PA protects the stomach from colonisation by H. pylori.[3, 4] Other studies showed that PA patients had high prevalence of H. pylori antibodies with low H. pylori staining in gastric mucosa reflecting a previous or hidden H. pylori infection which may have led to an H. pylori-driven autoimmune corpus atrophy.[5, 6]

In a previous work we showed that features which should help to discriminate between autoimmune and not autoimmune gastritis, like positivity to intrinsic factor and parietal cells antibodies, presence of ECL cell hyperplasia, pernicious anaemia and active H. pylori infection were similar in patients with corpus-restricted atrophic gastritis compared with those with antral and corporal atrophic gastritis,[7] thus indicating that the specific clinical-histological features associated with autoimmune gastritis are far from being well defined. Actually, this systematic review focused on PA only, and the topics related to aetiology of autoimmune gastritis and the role of H. pylori infection are beyond its aim.

However, we agree that the paucity of available literature emphasises the need for prospective studies to confirm the risk of GC associated with PA, which may also investigate associated host and environmental risk factors, as H. pylori infection.


The authors' declarations of personal and financial interests are unchanged from those in the original article.2