Strength in Numbers: Identifying a Significant Association between High Serum Ferritin Levels and Newly Diagnosed Malignancy in a Large Health Organization Cohort

Background: Ferritin, an iron storage protein and acute phase reactant, has been implicated in various aspects of human health and disease, including cancer. Previous studies have identified elevated serum ferritin (SF) levels in several cancer types, but a comprehensive examination across different malignancies remains lacking. This study aims to fill this gap by utilizing anonymized data from Maccabi Health Services (MHS), one of Israel's largest health organizations, to explore the association between elevated SF levels and the diagnosis of different malignancies. Methods: An extensive dataset from MHS, comprising 2.7 million members, including 1.3 million individuals who underwent SF level testing, was analyzed. ORs and 95% confidence intervals were calculated to assess the association between high SF levels and cancer diagnosis. Subgroup analysis was conducted to investigate variations across different malignancies. Results: The analysis revealed a significant association between elevated SF levels and cancer diagnosis among MHS members, with an OR of 1.9 (95% confidence interval, 1.71- 2.15). Subgroup analysis unveiled differences in the association across malignancy types, with hematologic, hepatobiliary, and respiratory malignancies more strongly associated with high SF levels. Conclusions: This study provides further support for the link between elevated SF levels and malignancy, leveraging a vast dataset from MHS, underscoring potential utilities of elevated SF levels as a potential indicator for cancer with a variable role among different malignancy types. Impact: The identification of elevated SF levels as a potential indicator for underlying malignancy for seemingly healthy individuals.