Risk of cancers of the oesophagus and stomach by histology or subsite in patients hospitalised for pernicious anaemia

Background: Although pernicious anaemia is an established risk factor for stomach cancer, data by anatomical subsite are not available. Moreover, a previous suggestion of a link to increased risk of oesophageal cancer needs further exploration. Methods: We followed 21 265 patients hospitalised for pernicious anaemia in Sweden from 1965 to 1999 for an average of 7.1 years. Standardised incidence ratio ( SIR) adjusted for sex, age, and calendar year was used to estimate relative risk, using the Swedish nationwide cancer incidence rates as reference. Results: Significant excess risks for squamous cell carcinoma of the oesophagus, and stomach cancer distal to the cardia, were observed in pernicious anaemia patients ( SIR 3.3 (95% confidence interval (CI) 2.4 - 4.4); SIR 2.4 ( 95% CI 2.1 - 2.7), respectively). The excess risks increased with increasing follow up duration. Among distal stomach cancers, the most conspicuous excess risk was for carcinoid tumours ( SIR 26.4 ( 95% CI 14.8 - 43.5)). Compared with the general population, no significant increased risk was observed for adenocarcinoma of the oesophagus ( SIR 1.7 ( 95% CI 0.7 - 3.4)) or gastric cardia ( SIR 1.2 ( 95% CI 0.6 - 2.0)). Conclusions: Achlorhydria following type A atrophic gastritis is associated with an elevated risk of adenocarcinoma of the non-cardia stomach, and surprisingly, with a risk of oesophageal squamous cell carcinoma. In contrast, no significant association, either positive or negative, was found with oesophageal or cardia adeoncarcinoma. The mechanism for the observed increased risk of oesophageal squamous cell carcinoma warrants further study.