Clinical study
Iron deficiency and gastrointestinal malignancy: a population-based cohort study

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Abstract

Purpose

We investigated whether iron deficiency, with or without anemia, is associated with an increased likelihood of gastrointestinal malignancy.

Subjects and methods

Data were obtained from the first National Health and Nutrition Examination Survey and Epidemiologic Followup Study, a nationally representative, prospective cohort study that measured hemoglobin levels and iron saturation and recorded follow-up diagnoses. We included persons 25 to 74 years of age with no previous gastrointestinal malignancy. Anemia was defined as a hemoglobin value below the fifth percentile for each age group and sex. Iron deficiency was defined as an iron saturation below 15%.

Results

Eighteen (0.2%) gastrointestinal malignancies were identified among the 9024 participants during the first 2 years of follow-up. None of the 442 premenopausal women with iron deficiency (92 with anemia and 350 without anemia) were diagnosed with gastrointestinal malignancy. Among men and postmenopausal women, the proportion diagnosed with gastrointestinal malignancy was 31 times greater (95% confidence interval [CI]: 9 to 107) in those with iron deficiency anemia (3/51 [6%]) and five times greater (95% CI: 1 to 21) in those with iron deficiency without anemia (2/223 [1%]), compared with those with normal hemoglobin levels and iron saturation (11/5733 [0.2%]).

Conclusion

Gastrointestinal malignancy is uncommon in iron-deficient premenopausal women with or without anemia. Among men and postmenopausal women, gastrointestinal malignancy is significantly more common in those with iron deficiency than in persons with normal serum iron saturation and hemoglobin levels.

Section snippets

Survey design and sample

The NHANES I was conducted between 1971 and 1974 on a nationwide probability sample of the civilian, noninstitutionalized population of the United States 9, 10. The survey included 14,407 participants aged 25 to 74 years who completed extensive questionnaires and had a physical examination and laboratory investigations. The NHEFS (11) attempted to locate these participants between 1982 and 1984 and to collect data on specific health conditions that had developed in the intervening period using

Results

Of the 9024 participants in this cohort, 716 (8%) were iron deficient, including 143 (1.6%) who were also anemic (Table 2 ). Eighteen participants (0.2%) were diagnosed with gastrointestinal malignancy during the 2-year period after the iron saturation and hemoglobin measurement. In 14 of these persons, the diagnosis was confirmed by hospital records; in the remaining 4 participants, it was based on information provided by the death certificate. There were 13 cancers of the colon or rectum,

Discussion

Previous studies 1, 2, 3, 4, 5, 8, 17, 18, 19 have emphasized the importance of iron deficiency anemia as a marker for occult gastrointestinal malignancy. However, it is likely that these studies overestimated the prevalence of these malignancies in persons with iron deficiency anemia (7), because almost all of these studies recruited patients who were referred to gastroenterology services for endoscopic evaluation. Indeed, in these prior studies, the mean hemoglobin level of patients

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1

Drs. Ioannou and Bryson are fellows at the Health Services Research and Development Program of the Veterans Affairs Puget Sound Health Care System, Seattle, Washington.

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