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. 5; 3 (2): 131-137. ©5 Annals of Family Medicine, Inc.

AbstractPurpose: Transferrin saturation of more than 60% has been identified as a cancer risk factor. It is unclear whether dietary iron intake increases the risk of cancer among individuals with transferrin saturation of less than 60%. The purpose of this study was to examine the association of dietary iron intake and the risk of cancer among adults with increased transferrin saturation.
Methods: Analysis of a cohort study, the National Health and Nutrition Examination Survey I Epidemiologic Follow-Up Study, was performed. US adults (aged 25 to 74 years at baseline) were followed up from baseline in 1971-1974 to 1992 (N = 6,309).
Results: A total of 7.3% of the US population had a serum transferrin saturation of more than 45% at baseline. Intake of dietary iron was essentially uncorrelated with transferrin saturation ( r = 0.04). Compared with individuals who had normal serum transferrin saturation and low dietary iron intake, individuals whose serum transferrin saturation was more than 45% and who had high dietary iron intake also had an increased adjusted relative risk of cancer (2.24; 95% confidence interval [CI], 1.02-4.89). Increased risk was not found for individuals with a transferrin saturation of more than 45% but a normal dietary iron intake (hazard ratio, 1.02; 95% CI, 0.69-1.49). Transferrin saturation levels could be set as low as 41%, and the individuals with high transferrin saturation and high dietary iron intake would still have an increased adjusted relative risk of cancer (hazard ratio, 2.00; 95% CI, 1.04-3.82).
Conclusions: Among persons with increased transferrin saturation, a daily intake of dietary iron more than 18 mg is associated with an increased risk of cancer. Future research might focus on the benefits of dietary changes in those individuals with increased serum transferrin saturation.


Recent evidence has suggested that increased body iron stores, as indicated by high percentages of transferrin saturation, may be associated with an increased risk for mortality. In cohort studies, increased transferrin saturation is associated with an increased all-cause mortality risk, even after controlling for common mortality risk factors.[1,2] The mortality risk associated with increased transferrin saturation is higher when those with increased transferrin saturation have an additional attribute that may interact with iron stores to potentially increase oxidative stress.[3,4] For example, persons with increased transferrin saturation who consume high levels of dietary iron or red meat have an increased mortality risk, whereas the risk is not increased for persons with high transferrin saturation but a normal dietary intake of iron or red meat.[2]

In addition to an increased all-cause mortality risk with increased transferrin saturation, research has shown a weak positive association between the percentage of transferrin saturation and the risk of cancer.[5,6] In one study in the United States, a significant trend was found for the risk of cancer among men that increased with each successive quartile of transferrin saturation.[5] The highest quartile of transferrin saturation (transferrin saturation levels of > 37%) did not have a significantly higher relative risk than the lowest quartile, however. Among both men and women, the risk of cancer was not significant until the transferrin saturation was at least 60%.[7]

In another study from Finland, the relative risk of cancer did not vary significantly between quartiles of transferrin saturation.[6] Persons with a transferrin saturation level of 60%, which corresponded to the 97th percentile, however, had a significantly increased risk of any type of cancer, as well as colorectal cancer.

The data relating transferrin saturation to cancer risk suggest that high levels of transferrin saturation, consistent with a predisposition to iron overload, increase a person´s risk.[8] It is unclear whether the cancer risk associated with elevated transferrin saturation is increased by consumption of high levels of dietary iron in the same manner as the association with mortality. Moreover, few data exist to indicate whether consumption of high amounts of dietary iron among persons with lower transferrin saturation carries an increased cancer risk. Thus, the purpose of this study was to examine, in a nationally representative cohort, the risk of cancer among persons with increased transferrin saturation who consumed high levels of dietary iron.