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

Abstract

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.

Pernicious anaemia and cancer risk in Denmark

“…In this cohort study of patients with PA we found a two-fold increase in the risk for stomach cancer in accordance with previous estimates (Blackburn et al, 1968;Brinton et al, 1989;Hsing et al, 1993). Our finding of an excess of cancer of the buccal cavity and pharynx is consistent with findings in the two large US and Swedish studies (Brinton et al, 1989;Hsing et al, 1993).…”

“…Our finding of an excess of cancer of the buccal cavity and pharynx is consistent with findings in the two large US and Swedish studies (Brinton et al, 1989;Hsing et al, 1993). We have no information on important risk factors such as alcohol intake and smoking habits but two cases of buccal cavity and pharynx cancer had mention of alcoholism in the hospital record.…”

“…Such changes, however, are not reflected in excess risks of small intestine and haematopoietic cancers comparable to those of buccal cavity, pharynx and stomach cancers. Risks for some lymphatic and haematological cancers were increased but not significantly as in previous investigations (Brinton et al, 1989;Hsing et al, 1993). The reason for the difference between results may be that we, in contrast to the previous studies, excluded the first year of follow-up, where there was an accumulation of non-Hodgkin's lymphoma, multiple myeloma and myeloid leukaemia in our study.…”

“…Several previous studies have documented an increased incidence of stomach cancer in patients with pernicious anaemia (PA) (Blackburn et al, 1968;Elsborg and Mosbech, 1979;Borch et al, 1988;Brinton et al, 1989;Hsing et al, 1993). An increase in the risk for other upper gastrointestinal cancers such as buccal cavity and pharynx (Brinton et al, 1989;Hsing et al, 1993) and oesophagus (Hsing et al, 1993) has also been reported, as well as increases for other digestive organ cancers [liver, biliary tract and pancreas (Hsing et al, 1993)], though these cancers have been investigated less extensively among PA patients than stomach cancer.…”

“…An increase in the risk for other upper gastrointestinal cancers such as buccal cavity and pharynx (Brinton et al, 1989;Hsing et al, 1993) and oesophagus (Hsing et al, 1993) has also been reported, as well as increases for other digestive organ cancers [liver, biliary tract and pancreas (Hsing et al, 1993)], though these cancers have been investigated less extensively among PA patients than stomach cancer. Of possible relevance to the autoimmune process in PA, studies in the US (Brinton et al, 1989) and Sweden (Hsing et al, 1993) have also reported increased risks for multiple myeloma and myeloid leukaemia.…”