Abstract 3596: Risk of gastrointestinal cancer by sex and age in U.S. veterans with new-onset iron deficiency anemia

Abstract Background: New onset iron deficiency anemia (IDA) may indicate undiagnosed gastrointestinal (GI) cancer. Current guidelines strongly recommend colonoscopy and upper endoscopy (bidirectional endoscopy) for new onset IDA in men and postmenopausal women. In younger women, guidelines conditionally recommend bidirectional endoscopy, as IDA can occur from benign menstrual blood loss. Given rising rates of GI cancers in younger individuals, disregarding IDA in premenopausal women could inadvertently lead to delayed diagnoses of GI cancer. We assessed the likelihood of GI cancer in a national cohort of Veterans with new onset IDA by age and sex, using common clinical cutoffs. Methods: We conducted a retrospective cohort study in the Veterans Health Administration (VA). We identified regular users of VA primary care (≥1 primary care visit every 2 years over a 5-year period) who developed a new anemia (hemoglobin <12 g/dL for women, <13 g/dL for men), and who had a ferritin within 1 year. We defined IDA as ferritin <45 ng/ml and varied this definition in sensitivity analysis. We identified luminal GI cancers (esophageal, gastric, small intestine, colon, rectum) diagnosed within 1 year of incident anemia by the VA cancer registry. We calculated the odds ratio (OR) of IDA and a GI cancer diagnosis in the overall cohort, stratified by age and sex. Results: 308,250 individuals met inclusion criteria, with 18,672 (6.1%) women and 289,578 (93.9%) men. 94,713 (30.7%) had IDA, and 33,711 (10.9%) were <50 years old. 3,035 GI cancers were diagnosed within 1 year of incident anemia (0.98%), the majority of which were colon cancers (n=1835, 60.5%). The odds of cancer were significantly higher in those with IDA versus non-IDA (OR 4.47, 95% CI: 4.14-4.82). For women with IDA age ≥ 50 compared to those < age 50, the OR of GI cancer in 1 year was 6.62 (95% CI: 3.54-12.36). In those < age 50 with IDA, men had an OR of GI cancer in 1 year of 9.74 compared to women (95% CI: 5.45-17.40). In those age ≥ 50 with IDA, men had an OR of GI cancer of 2.24 compared to women (95% CI: 1.64-3.05). In sensitivity analysis, lowering the ferritin cutoff to 10 ng/ml did not change the directionality of these relationships. Conclusions: Women age < 50 with new onset IDA were substantially less likely to develop GI cancer than comparable age men and older women. These findings support current guidelines, which strongly recommend bidirectional endoscopy in men and postmenopausal women and conditionally recommend endoscopy in premenopausal women. At the same time, clinicians should carefully assess for the presence / absence of symptoms that point to GI tract blood loss in premenopausal women. Additionally, future work should explore the role of computational methods and the electronic health record to leverage data from longitudinal complete blood counts (CBCs), moving beyond simple ferritin cutoffs. Citation Format: Andrew J. Read, Sarah L. Krein, Tony Van, Kennedy Dubose, Jennifer Burns, Akbar K. Waljee, Sameer D. Saini. Risk of gastrointestinal cancer by sex and age in U.S. veterans with new-onset iron deficiency anemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3596.