There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Excess iron has been implicated in cancer risk through increased iron-catalyzed free radical-mediated oxidative stress. A multicenter randomized, controlled, single-blinded clinical trial (VA Cooperative Study #410) tested the hypothesis that reducing iron stores by phlebotomy would influence vascular outcomes in patients with peripheral arterial disease. Patients without a visceral malignancy in the last 5 years (n = 1277) were randomly assigned to control (n = 641) or iron reduction (n = 636). Occurrence of new visceral malignancy and cause-specific mortality data were collected prospectively. Cancer and mortality outcomes in the two arms were compared using intent-to-treat analysis with a Cox proportional hazards regression model. Statistical tests were two-sided. Patients were followed up for an average of 4.5 years. Ferritin levels were similar in both groups at baseline but were lower in iron reduction patients than control patients across all 6-month visits (mean = 79.7 ng/mL, 95% confidence interval [CI] = 73.8 to 85.5 ng/mL vs 122.5 ng/mL, 95% CI = 115.5 to 129.5 ng/mL; P < .001). Risk of new visceral malignancy was lower in the iron reduction group than in the control group (38 vs 60, hazard ratio [HR] = 0.65, 95% CI = 0.43 to 0.97; P = .036), and, among patients with new cancers, those in the iron reduction group had lower cancer-specific and all-cause mortality (HR = 0.39, 95% CI = 0.21 to 0.72; P = .003; and HR = 0.49, 95% CI = 0.29 to 0.83; P = .009, respectively) than those in the control group. Mean ferritin levels across all 6-monthly visits were similar in patients in the iron reduction and control groups who developed cancer but were lower among all patients who did not develop cancer than among those who did (76.4 ng/mL, 95% CI = 71.4 to 81.4 ng/mL, vs 127.1 ng/mL, 95% CI = 71.2 to 183.0 ng/mL; P = .017). Iron reduction was associated with lower cancer risk and mortality. Further studies are needed to define the role of body iron in cancer risk.

Related collections

Most cited references 24

Record: found
Abstract: found
Article: not found

Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer.

Timothy Winton, Robert A. Livingston, David. Johnson … (2005)

We undertook to determine whether adjuvant vinorelbine plus cisplatin prolongs overall survival among patients with completely resected early-stage non-small-cell lung cancer. We randomly assigned patients with completely resected stage IB or stage II non-small-cell lung cancer to vinorelbine plus cisplatin or to observation. The primary end point was overall survival; principal secondary end points were recurrence-free survival and the toxicity and safety of the regimen. A total of 482 patients underwent randomization to vinorelbine plus cisplatin (242 patients) or observation (240); 45 percent of the patients had pathological stage IB disease and 55 percent had stage II, and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. In both groups, the median age was 61 years, 65 percent were men, and 53 percent had adenocarcinomas. Chemotherapy caused neutropenia in 88 percent of patients (including grade 3 febrile neutropenia in 7 percent) and death from toxic effects in two patients (0.8 percent). Nonhematologic toxic effects of chemotherapy were fatigue (81 percent of patients), nausea (80 percent), anorexia (55 percent), vomiting (48 percent), neuropathy (48 percent), and constipation (47 percent), but severe (grade 3 or greater) toxic effects were uncommon (<10 percent). Overall survival was significantly prolonged in the chemotherapy group as compared with the observation group (94 vs. 73 months; hazard ratio for death, 0.69; P=0.04), as was relapse-free survival (not reached vs. 46.7 months; hazard ratio for recurrence, 0.60; P<0.001). Five-year survival rates were 69 percent and 54 percent, respectively (P=0.03). Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non-small-cell lung cancer. Copyright 2005 Massachusetts Medical Society.

0 comments Cited 327 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Iron overload and its association with cancer risk in humans: evidence for iron as a carcinogenic metal.

Xi Huang (2003)

Unlike arsenic, chromium, or nickel, the carcinogenicity of iron is still under debate. In this review, evidence for iron as a carcinogenic metal was summarized from epidemiological, animal, and cell culture studies. The role of iron in various cancers, such as colorectal cancer and liver cancer was presented. Recent advancements on the molecular mechanisms of iron carcinogenesis were also reviewed. These include: (1) iron autoxidation involving only Fe(2+)+O2 in oxidant formation in biological systems and its pH dependency; (2) activation of oxidative responsive transcription factors and pro-inflammatory cytokines; and (3) iron-induced hypoxia signaling.

0 comments Cited 88 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Iron chelators with high antiproliferative activity up-regulate the expression of a growth inhibitory and metastasis suppressor gene: a link between iron metabolism and proliferation.

Nghia T V Le, Minh T N Le (2004)

Iron (Fe) is critical for proliferation, but its precise role in cell cycle progression remains unclear. In this study, we examined the mechanisms involved by assessing the effects of Fe chelators on the expression of molecules that play key roles in this process. In initial studies, gene arrays were used to assess gene expression after incubating cells with 2 Fe chelators, namely, desferrioxamine (DFO) and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), or the DNA-damaging agent, actinomycin D. From the genes assessed, only the N-myc downstream-regulated gene 1 (Ndrg1) was specifically up-regulated by Fe chelation. Although the function of Ndrg1 is unclear, previous studies showed it markedly slows tumor growth and acts as a potent metastasis suppressor. Incubation of cells with chelators markedly increased Ndrg1 mRNA and protein expression, but this was not found with their Fe complexes or when the Fe-binding site had been inactivated. Increased Ndrg1 expression following Fe chelation was related to the permeability and antiproliferative activity of chelators and could be reversed by Fe repletion. Moreover, Ndrg1 up-regulation after chelation occurred at the transcriptional level and was mediated by hypoxia inducible factor-1alpha (HIF-1alpha)-dependent and -independent mechanisms. Our investigation suggests Ndrg1 is a novel link between Fe metabolism and the control of proliferation.