Pernicious anemia and subsequent cancer. A population-based cohort study.

Background: Elevated risk of cancers of the stomach, colon, and buccal cavity, as well as of lymphoma and leukemia, have been reported for patients with pernicious anemia in case reports and hospital-based and cross-sectional studies.
Methods: A cohort of 2021 men and 2496 women living in the Uppsala health care region in Sweden, discharged with a hospital diagnosis of pernicious anemia from 1965 to 1983, was followed for 20 years for subsequent risk of cancer.
Results: A total of 553 cancers were diagnosed among these patients, significantly more than expected based on cancer standardized incidence rates (SIRs) in the general population (SIR = 1.4; 95% confidence interval [CI], 1.2-1.5). Most prominent were excesses for cancer of the stomach (SIR = 2.9; 95% CI, 2.4-3.5), esophagus (SIR = 3.2; 95% CI, 1.8-5.2), and pancreas (SIR = 1.7; 95% CI, 1.2-2.4) among men and women; myeloid leukemia among men (SIR = 4.4; 95% CI, 1.8-5.2); and multiple myeloma among women (SIR = 2.5; 95% CI, 1.1-4.9). An excess of gastric carcinoid tumors also was evident in this cohort. The risk of stomach cancer was highest in the first year after diagnosis of pernicious anemia (SIR = 7.4; 95% CI, 5.3-10.1), but an increased risk persisted throughout the follow-up period. The risk of esophageal cancer also remained elevated throughout the study period, although the risk of pancreatic cancer dropped off after 5 years.
Conclusions: This study confirms the excess risk of gastric carcinoma and carcinoid tumors associated with pernicious anemia, and suggests that the susceptibility state may extend to esophageal and other cancers.