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Background: Experimental studies suggest that iron overload might increase pancreatic cancer risk. We evaluated whether prediagnostic hemochromatosis and iron-overload diseases, including sideroblastic and congenital dyserythropoietic anemias, and non–alcoholic-related chronic liver disease (NACLD) were associated with pancreatic cancer risk in older adults. Methods: We conducted a population-based, case–control study within the U.S. Surveillance, Epidemiology, and End Results Program (SEER)-Medicare linked data. Incident primary pancreatic cancer cases were adults &amp;gt; 66 years. Controls were alive at the time cases were diagnosed and matched to cases (4:1 ratio) by age, sex, and calendar year. Hemochromatosis, iron-overload anemias, and NACLD were reported 12 or more months before pancreatic cancer diagnosis or control selection using Medicare claims data. Adjusted unconditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI) between hemochromatosis, sideroblastic and congenital dyserythropoietic anemias, NACLD, and pancreatic cancer. Results: Between 1992 and 2015, 80,074 pancreatic cancer cases and 320,296 controls were identified. Overall, we did not observe statistically significant associations between hemochromatosis, sideroblastic anemia, or congenital dyserythropoietic anemia and pancreatic cancer; however, sideroblastic anemia was associated with later primary pancreatic cancer (OR, 1.30; 95% CI, 1.03–1.64). NACLD was associated with first (OR, 1.10; 95% CI, 1.01–1.19), later (OR, 1.17; 95% CI, 1.02–1.35), and all (OR, 1.12; 95% CI, 1.04–1.20) pancreatic cancer. Conclusions: Overall hemochromatosis and iron-overload anemias were not associated with pancreatic cancer, whereas NACLD was associated with increased risk in this large study of older adults. Impact: These results partly support the hypothesis that iron-overload diseases increase pancreatic cancer risk.

Hemochromatosis, Iron Overload–Related Diseases, and Pancreatic Cancer Risk in the Surveillance, Epidemiology, and End Results (SEER)-Medicare