Heme iron, zinc and upper digestive tract cancer: The Iowa Women's Health Study

Abstract

We examined associations among dietary heme iron as a possible pro-oxidant, dietary zinc as a possible antioxidant, and the incidence of upper digestive tract cancer; 34,708 postmenopausal women, aged 55-69 years at baseline who completed a food frequency questionnaire, were followed 16 years. There were 75 upper digestive tract cancer cases (52 gastric cancer and 23 esophageal cancer). When heme iron and zinc were mutually adjusted, in dose-response manners, heme iron intake was positively associated with the risk of upper digestive tract cancer, while zinc intake was inversely associated with risk. After adjusting for age, total energy intake, cigarette smoking and alcohol consumption, relative risks for quintiles of heme iron intake were 1.0, 1.53, 2.15, 3.05 and 2.83 (p for trend 5 0.06) and corresponding relative risks for zinc intake were 1.0, 0.86, 0.42, 0.37 and 0.13 (p for trend < 0.01). Additional adjustment for body mass index, physical activity, hormone replacement therapy, multivitamin intake and intake of saturated fat, vitamin C, vitamin E and folate did not change the results. Higher intake of heme iron is associated with higher risk, while higher intake of zinc is associated with lower, risk of upper digestive tract cancer. ' 2005 Wiley-Liss, Inc.Key words: heme iron; zinc; esophageal cancer; gastric cancer; oxidative stress Although iron is vital for all living organisms, iron is also potentially carcinogenic due to its catalytic effect on the formation of hydroxyl radicals, suppression of the activity of host defense cells and promotion of cancer cell multiplication. 1,2 On the other hand, zinc has antioxidant properties; zinc ions may replace redox active molecules and may induce the synthesis of metallothionein, sulfhydryl-rich proteins that protect against free radicals. 3 At a molecular level, metals such as iron can substitute for zinc and may be responsible for metal-induced DNA damage and carcinogenesis, 4,5 suggesting a close interrelation of the 2 nutrients. Supporting these observations, we recently reported that intake of dietary heme iron, the most bioavailable form of iron, is associated with an increased risk of proximal colon cancer, while intake of dietary zinc is associated with a decreased risk of both proximal and distal colon cancer. 6 Even though various upper digestive tract cancers have been shown to be distinct entities in terms of many risk factors and pathological and/or clinical features, carcinogenesis due to oxidative stress is not a site-specific mechanism. Many known risk factors in carcinogenesis such as infection, inflammation, cigarette smoking, nutrition or alcohol consumption may ultimately be associated with oxidative stress as a unifying underlying mechanism. 7-10 For example, oxidative stress associated with inflammation plays an important role in gastric carcinogenesis as a mediator of carcinogenic compound formation, DNA damage and cell proliferation. 7 Similarly, oxidative stress also has been suggested to be a driving force in the pathogenesis of eso...

Contents of Endometriotic Cysts, Especially the High Concentration of Free Iron, Are a Possible Cause of Carcinogenesis in the Cysts through the Iron-Induced Persistent Oxidative Stress

“…ROS in biological systems induce oxidative stress and lead to iron-induced carcinogenesis (17). In humans, dietary iron is thought to be a risk for gastrointestinal cancers (29,30) and increased body iron stores are reported to associate with poor prognosis of several human malignant neoplasms (31 -34). Moreover, patients with genetic hemochromatosis had f200 times greater risk for primary hepatocellular carcinoma than the age-matched control population (35 -37).…”

Iron and Cancer Risk—A Systematic Review and Meta-analysis of the Epidemiological Evidence

“…The second limitation lies in the fact that heme iron intake is usually determined indirectly, using 2 possible methods. One method uses the 40% of total iron from meat (20,39,105) and the second method uses meat specific proportions: 69% for beef; 39% for pork, ham, bacon, pork-based luncheon meats, and veal; 26% for chicken and fish; and 21% for liver (37). Recently, Cross and colleagues created a heme iron database for meats according to meat type, cooking method, and doneness level (21).…”

“…We also excluded one article (20) that provided a combined effect estimate for different cancer types without referring to cancer-specific effects.…”

A comparative study of the iron status of patients with oesophageal adenocarcinoma to determine suitability for a clinical trial of iron chelation therapy

“…4,5 Of note, a high dietary intake of haem iron has been shown to correlate with increased OAC risk in humans. 6,7 Likewise, excess systemic iron has been shown to exacerbate oesophageal tumourigenesis in animal models.…”