Cancer of the upper gastrointestinal tract among patients with pernicious anemia: A case-cohort study

Background: An association between pernicious anemia and stomach cancer has been established in several studies. An increased risk of pancreatic and e sophageal cancers has also been reported among pernicious anemia patients. The aim of this case-cohort study was to identify additional risk factors f or cancer of the esophagus, stomach, and pancreas among patients with perni cious anemia. Methods: A population-based cohort of 4586 patients with pern icious anemia was linked to the Swedish Cancer Registry to identify patient s who subsequently developed cancers of the esophagus, stomach, or pancreas using a case-cohort design. A subcohort consisting of 4% of the cohort was randomly selected to serve as the comparison group. Information on medical history, smoking habits, and alcohol use was retrieved from medical charts and analyzed for cancer patients and subcohort members. Results: We could not identify any risk factors other than pernicious anemia for stomach canc er. For pancreatic and esophageal cancer, younger age at diagnosis of perni cious anemia was associated with an increased risk. A prior gastric resecti on, smoking and alcohol abuse were more frequent among esophageal cancer ca ses than in the subcohort. Conclusions: We conclude that a causal relations hip between pernicious anemia and subsequent development of esophageal or p ancreatic cancers still remains unproven. For esophageal cancer, confoundin g by smoking and alcohol use is the likely explanation of earlier reports o f an association. In the case of stomach cancer, both the inflammatory proc ess, secondary to the pernicious anemia, and pernicious anemia per se may b e factors leading to malignant transformation.