Transferrin Saturation, Dietary Iron Intake, and Risk of Cancer

Arch G. Mainous III, PhD; James M. Gill, MD, MPH; Charles J. Everett, PhD


Ann Fam Med. 2005;3(2):131-137. 

In This Article


A total of 7.3% of the adult US population aged 25 to 74 years at baseline had serum transferrin saturations of more than 45%, and 16.5% of the adult population had iron ingestion of more than 18 mg/d. Serum transferrin saturation percentages and dietary iron intake had a weak Pearson correlation ( r = 0.04). Only 1.0% of the adult population had both increased serum transferrin saturation and high iron ingestion ( Table 1 ). Overall, 12.0% of the adult US population developed cancer between 4 and 18 years after the baseline examination.

The unadjusted relationships between cancer events, serum transferrin saturation more than 45%, and dietary iron intake are presented in Figure 1. Without adjustments, the Cox proportional hazards model analysis indicates that increased serum transferrin saturation did not significantly increase cancer risk ( Table 2 ). After adjustment for age, sex, race, smoking, BMI, and comorbidities at baseline, however, the group with increased serum transferrin saturation and high dietary iron intake had a relative risk of cancer (hazard ratio [HR]) 2.24 times more than that of the group with normal serum transferrin saturation and low dietary iron intake. The results of the Schoenfeld analysis indicated that the hazards were proportional. No significant interaction was found in the adjusted analyses by including transferrin saturation and dietary iron as continuous variables (HR, 1.00; 95% CI, 1.00–1.00) rather than categorizing them as low and high on the basis of previous clinically specified levels.

Population percentage cancer-free for normal vs elevated transferrin saturation (TS)> 45% and low vs high iron (Fe) intake.

When we examined dietary iron intake and the risk of cancer at varying levels of transferrin saturation, we found in adjusted models that for transferrin saturation of 40% and dietary iron intake of 18 mg/d, the risk of cancer was not significant (HR, 1.60; 95% CI, 0.83–3.06). A significant risk, however, was found at transferrin saturation levels of more than 41% (HR, 2.00; 95% CI, 1.04–3.82), and a transferrin saturation of more than 43% yielded the highest risk of cancer when dietary iron was more than 18 mg/d (HR, 2.32; 95% CI, 1.21–4.42). At more than 50% transferrin saturation, the sample in the high transferrin saturation and high dietary iron group becomes too small to make reliable population estimates.


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