Original article
Alimentary tract
Cancer Risk After Pernicious Anemia in the US Elderly Population

https://doi.org/10.1016/j.cgh.2015.05.040Get rights and content

Background & Aims

Pernicious anemia, a result of autoimmune gastritis, is the most common cause of vitamin B12 deficiency, affecting 2% to 5% of the elderly population. Treatment with vitamin B12 cures the anemia, but not the gastritis. Findings from small studies have indicated that patients with pernicious anemia could have an increased risk of cancer.

Methods

We performed a population-based, case–control study of individuals in the Surveillance, Epidemiology, and End Results–Medicare database, comparing 1,138,390 cancer cases (age, 66–99 y) with 100,000 matched individuals without cancer (controls). Individuals with pernicious anemia were identified based on their medical claims within the year before selection for the study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, and models were adjusted for sex, age, and calendar year of diagnosis and selection.

Results

Compared with controls, we found individuals with pernicious anemia to be at increased risk for noncardia gastric adenocarcinoma (OR, 2.18; 95% CI, 1.94–2.45) and gastric carcinoid tumors (OR, 11.43; 95% CI, 8.90–14.69). In addition, people with pernicious anemia have an increased risk of developing tonsilar cancer (OR, 2.00; 95% CI, 1.40–2.85), hypopharyngeal cancer (OR, 1.92; 95% CI, 1.35–2.73), esophageal squamous cell carcinoma (OR, 2.12; 95% CI, 1.76–2.55), small intestinal cancer (OR, 1.63; 95% CI, 1.32–2.02), liver cancer (OR, 1.49; 95% CI, 1.28– 1.73), myeloma (OR, 1.55; 95% CI, 1.37–1.75), acute myeloid leukemia (OR, 1.68; 95% CI, 1.46–1.93), and myelodysplastic syndrome (OR, 2.87; 95% CI, 2.53–3.26). People with pernicious anemia have a lower risk of rectal cancer than the general population (OR, 0.82; 95% CI, 0.74– 0.92).

Conclusions

In a population-based, case–control study of individuals in the Surveillance, Epidemiology, and End Results–Medicare database, we found individuals with pernicious anemia to have significantly increased risks of gastric carcinoid tumors, adenocarcinomas, and other cancers located throughout the body.

Section snippets

Surveillance, Epidemiology, and End Results–Medicare Data Sources

SEER is a National Cancer Institute–funded program collecting data on cancer incidence and survival from 17 US cancer registries (http://www.seer.cancer.gov), covering approximately 26% of the US population. Medicare provides federally funded health insurance for approximately 97% of persons aged 65 years and older in the United States, as well as for individuals younger than age 65 years who have a medical disability. Hospital inpatient care is included in Part A coverage, which all

Results

The characteristics of cases and controls are presented in Table 1. Cases and controls were matched on sex, age, and calendar year of case diagnosis/control selection.

Pernicious anemia was reported in 1.5% of cancer cases and controls and 66% of those identified with pernicious anemia (both cases and controls) had a record of B12 treatment (data not shown). A slightly increased risk of all cancer was observed for subjects with pernicious anemia, relative to controls (OR, 1.07; 95% CI,

Discussion

We used a very large case–control study to investigate the association between pernicious anemia and cancer. Consistent with previous, far smaller, studies,6, 7, 8, 9, 17 we noted a statistically significant increase in the risk of several malignancies, gastrointestinal and nongastrointestinal, for people with pernicious anemia. The large size of our study allowed us to explore many different cancer types by histology and subsite, whether associations differed by sex, in cases occurring close

Acknowledgments

The authors acknowledge the efforts of Brenda Edwards and Lynn Ries of the Surveillance Research Program, National Cancer Institute; the Office of Research, Development, and Information, Centers for Medicare and Medicaid Services; Information Management Services, Inc; and the Surveillance, Epidemiology, and End Results Program tumor registries in the creation of the Surveillance, Epidemiology, and End Results–Medicare database.

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    Conflicts of interest The authors disclose no conflicts.

    Funding This work was supported by the Intramural Research Program of the National Cancer Institute at the US National Institutes of Health.

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