Associations of Serum Ferritin and Transferrin % Saturation With All-cause, Cancer, and Cardiovascular Disease Mortality: Third National Health and Nutrition Examination Survey Follow-up Study

Abstract

Objectives Even though experimental studies have suggested that iron can be involved in generating oxidative stress, epidemiologic studies on the association of markers of body iron stores with cardiovascular disease or cancer remain controversial. This study was performed to examine the association of serum ferritin and transferrin saturation (%TS) with all-cause, cancer, and cardiovascular mortality. Methods The study subjects were men aged 50 years or older and postmenopausal women of the Third National Health and Nutrition Examination Survey 1988-1994. Participants were followed-up for mortality through December 31, 2006. Results Serum ferritin was not associated with all-cause, cancer, or cardiovascular mortality for either men or postmenopausal women. However, all-cause, cancer, and cardiovascular mortality were inversely associated with %TS in men. Compared with men in the lowest quintile, adjusted hazard ratios for all-cause, cancer, and cardiovascular mortality were 0.85, 0.86, 0.76, and 0.74 ( p for trend < 0.01), 0.82, 0.73, 0.75, and 0.63 ( p for trend < 0.01), and 0.86, 0.81, 0.72, and 0.76 ( p for trend < 0.01), respectively. For postmenopausal women, inverse associations were also observed for all-cause and cardiovascular mortality, but cancer mortality showed the significantly lower mortality only in the 2nd quintile of %TS compared with that of the 1st quintile. Conclusions Unlike speculation on the role of iron from experimental studies, %TS was inversely associated with all-cause, cancer and cardiovascular mortality in men and postmenopausal women. On the other hand, serum ferritin was not associated with all-cause, cancer, or cardiovascular mortality.

Quantitative data on the magnitude of the systemic inflammatory response and its relationship with serum measures of iron status

“…[18][19] Given that CRP and albumin also predict mortality from any cause, cancer, cardiovascular disease and cerebrovascular causes, it may be that the association of measures of iron status and mortality is dependent on the presence of systemic inflammation. 20 Further work is required to test this hypothesis.…”

Targeting iron metabolism in drug discovery and delivery

“…Although several studies have indeed shown a correlation between the incidence and mortality of cancer and systemic iron levels, as measured by transferrin saturation or serum ferritin, this correlation is generally not strong, has shown conflicting outcomes, and it is often confounded by the presence of other pathology88,89. There is, however, clear evidence that deregulated iron homeostasis on a local — that is, microenvironmental and/or cellular — level is associated with tumour progression, as illustrated by changes in expression of iron-related genes in cancer cells (Figure 4), the levels of which are inversely correlated with patient survival90–92.…”

High preoperative serum ferritin predicted poor prognosis in non-metastatic colorectal cancer

“…Serum ferritin was not prognostic in melanoma patients treated with adjuvant interferon-alfa,16 nor in operable breast cancer 17. Population based epidemiological research also did not support the association of serum ferritin with cancer mortality either 18,19. It seems that the prognostic significance of serum iron metabolism parameters is dependent on both tumor-type and clinical context.…”