Cancer Causes & Control

, Volume 21, Issue 12, pp 2269–2279

Iron intake and markers of iron status and risk of Barrett’s esophagus and esophageal adenocarcinoma

  • Mark G. O’Doherty
  • Christian C. Abnet
  • Liam J. Murray
  • Jayne V. Woodside
  • Lesley A. Anderson
  • John D. Brockman
  • Marie M. Cantwell
Original paper

Abstract

Objective

To investigate the association between iron intake and iron status with Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC).

Methods

A total of 220 BE patients, 224 EAC patients, and 256 frequency-matched controls completed a lifestyle and food frequency questionnaire and provided serum and toenail samples between 2002 and 2005. Using multiple logistic regression, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated within quartiles of intake/status.

Results

Comparing the fourth to the first quartile, ferritin (OR 0.47; 95% CI: 0.23, 0.97) and transferrin saturation (OR 0.41; 95% CI: 0.20, 0.82) were negatively associated with BE; while total iron binding capacity was positively associated per 50 μg/dl increment (OR 1.47; 95% CI: 1.12, 1.92). Comparing the fourth to the first quartile, iron intake (OR 0.50; 95% CI: 0.25, 0.98), non-heme iron intake per 10 mg/day increment (OR 0.29; 95% CI: 0.08, 0.99), and toenail iron (OR 0.40; 95% CI: 0.17, 0.93) were negatively associated with EAC; while heme iron intake was positively associated (OR 3.11 95% CI: 1.46, 6.61).

Principal conclusion

In contrast to the hypothesis that increased iron intakes and higher iron stores are a risk factor for BE and EAC, this study suggests that higher iron intakes and stores may have a protective association with BE and EAC, with the exception of what was found for heme iron intake.

Keywords

Adenocarcinoma Barrett’s esophagus Epidemiology Ferritin Iron 

References

  1. 1.
    Bosetti C, Levi F, Ferlay J et al (2008) Trends in oesophageal cancer incidence and mortality in Europe. Int J Cancer 122:1118–1129CrossRefPubMedGoogle Scholar
  2. 2.
    Eloubeidi MA, Mason AC, Desmond RA, El-Serag HB (2003) Temporal trends (1973–1997) in survival of patients with esophageal adenocarcinoma in the United States: a glimmer of hope? Am J Gastroenterol 98:1627–1633PubMedGoogle Scholar
  3. 3.
    Brown LM, Devesa SS (2002) Epidemiologic trends in esophageal and gastric cancer in the United States. Surg Oncol Clin N Am 11:235–256CrossRefPubMedGoogle Scholar
  4. 4.
    Blot WJ, McLaughlin JK (1999) The changing epidemiology of esophageal cancer. Semin Oncol 26:2–8PubMedGoogle Scholar
  5. 5.
    di Pietro M, Peters CJ, Fitzgerald RC (2008) Clinical puzzle: Barrett’s oesophagus. Dis Model Mech 1:26–31CrossRefPubMedGoogle Scholar
  6. 6.
    Jankowski JA, Harrison RF, Perry I, Balkwill F, Tselepis C (2000) Barrett’s metaplasia. Lancet 356:2079–2085CrossRefPubMedGoogle Scholar
  7. 7.
    Shaheen NJ, Crosby MA, Bozymski EM, Sandler RS (2000) Is there publication bias in the reporting of cancer risk in Barrett’s esophagus? Gastroenterology 119:333–338CrossRefPubMedGoogle Scholar
  8. 8.
    Henle ES, Luo Y, Gassmann W, Linn S (1996) Oxidative damage to DNA constituents by iron-mediated fenton reactions. The deoxyguanosine family. J Biol Chem 271:21177–21186CrossRefPubMedGoogle Scholar
  9. 9.
    Ullen H, Augustsson K, Gustavsson C, Steineck G (1997) Supplementary iron intake and risk of cancer: reversed causality? Cancer Lett 114:215–216CrossRefPubMedGoogle Scholar
  10. 10.
    Chen X, Ding YW, Yang G, Bondoc F, Lee MJ, Yang CS (2000) Oxidative damage in an esophageal adenocarcinoma model with rats. Carcinogenesis 21:257–263CrossRefPubMedGoogle Scholar
  11. 11.
    Chen X, Yang G, Ding WY, Bondoc F, Curtis SK, Yang CS (1999) An esophagogastroduodenal anastomosis model for esophageal adenocarcinogenesis in rats and enhancement by iron overload. Carcinogenesis 20:1801–1808CrossRefPubMedGoogle Scholar
  12. 12.
    Goldstein SR, Yang GY, Chen X, Curtis SK, Yang CS (1998) Studies of iron deposits, inducible nitric oxide synthase and nitrotyrosine in a rat model for esophageal adenocarcinoma. Carcinogenesis 19:1445–1449CrossRefPubMedGoogle Scholar
  13. 13.
    Fracanzani AL, Conte D, Fraquelli M et al (2001) Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non-iron-related chronic liver disease. Hepatology 33:647–651CrossRefPubMedGoogle Scholar
  14. 14.
    Elmberg M, Hultcrantz R, Ekbom A et al (2003) Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives. Gastroenterology 125:1733–1741CrossRefPubMedGoogle Scholar
  15. 15.
    Geier D, Hebert B, Potti A (2002) Risk of primary non-hepatocellular malignancies in hereditary hemochromatosis. Anticancer Res 22:3797–3799PubMedGoogle Scholar
  16. 16.
    Grant WB (2008) An ecological study of cancer mortality rates including indices for dietary iron and zinc. Anticancer Res 28:1955–1963PubMedGoogle Scholar
  17. 17.
    Lee DH, Anderson KE, Folsom AR, Jacobs DR Jr (2005) Heme iron, zinc and upper digestive tract cancer: the Iowa women’s health study. Int J Cancer 117:643–647CrossRefPubMedGoogle Scholar
  18. 18.
    Zhang ZF, Kurtz RC, Yu GP et al (1997) Adenocarcinomas of the esophagus and gastric cardia: the role of diet. Nutr Cancer 27:298–309CrossRefPubMedGoogle Scholar
  19. 19.
    Wolfgarten E, Rosendahl U, Nowroth T et al (2001) Coincidence of nutritional habits and esophageal cancer in Germany. Onkologie 24:546–551CrossRefPubMedGoogle Scholar
  20. 20.
    Corley DA, Kubo A, Levin TR et al (2008) Iron intake and body iron stores as risk factors for Barrett’s esophagus: a community-based study. Am J Gastroenterol 103:2997–3004CrossRefPubMedGoogle Scholar
  21. 21.
    Anderson LA, Johnston BT, Watson RG et al (2006) Nonsteroidal anti-inflammatory drugs and the esophageal inflammation-metaplasia-adenocarcinoma sequence. Cancer Res 66:4975–4982CrossRefPubMedGoogle Scholar
  22. 22.
    Day N, Oakes S, Luben R et al (1999) EPIC-Norfolk: study design and characteristics of the cohort. European prospective investigation of cancer. Br J Cancer 80:95–103PubMedGoogle Scholar
  23. 23.
    Food Standards Agency (2002) McCance and Widdowson’s the composition of foods, 6th summary edn. Royal Society of Chemistry, Cambridge, UKGoogle Scholar
  24. 24.
    Balder HF, Vogel J, Jansen MC et al (2006) Heme and chlorophyll intake and risk of colorectal cancer in the Netherlands cohort study. Cancer Epidemiol Biomarkers Prev 15:717–725CrossRefPubMedGoogle Scholar
  25. 25.
    Crawley H (1998) Food portion sizes. HMSO, London, UKGoogle Scholar
  26. 26.
    Garland M, Morris JS, Rosner BA et al (1993) Toenail trace element levels as biomarkers: reproducibility over a 6-year period. Cancer Epidemiol Biomarkers Prev 2:493–497PubMedGoogle Scholar
  27. 27.
    Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyzes. Am J Epidemiol 124:17–27PubMedGoogle Scholar
  28. 28.
    Pearson TA, Mensah GA, Alexander RW et al (2003) Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the centers for disease control and prevention and the American heart association. Circulation 107:499–511CrossRefPubMedGoogle Scholar
  29. 29.
    Hsing AW, McLaughlin JK, Olsen JH, Mellemkjar L, Wacholder S, Fraumeni JF Jr (1995) Cancer risk following primary hemochromatosis: a population-based cohort study in Denmark. Int J Cancer 60:160–162CrossRefPubMedGoogle Scholar
  30. 30.
    Lee DH, Anderson KE, Harnack LJ, Folsom AR, Jacobs DR Jr (2004) Heme iron, zinc, alcohol consumption, and colon cancer: Iowa women’s health study. J Natl Cancer Inst 96:403–407CrossRefPubMedGoogle Scholar
  31. 31.
    Kabat GC, Miller AB, Jain M, Rohan TE (2008) Dietary iron and heme iron intake and risk of endometrial cancer: a prospective cohort study. Br J Cancer 98:194–198CrossRefPubMedGoogle Scholar
  32. 32.
    Kabat GC, Miller AB, Jain M, Rohan TE (2007) Dietary iron and heme iron intake and risk of breast cancer: a prospective cohort study. Cancer Epidemiol Biomarkers Prev 16:1306–1308CrossRefPubMedGoogle Scholar
  33. 33.
    Kabat GC, Miller AB, Jain M, Rohan TE (2007) A cohort study of dietary iron and heme iron intake and risk of colorectal cancer in women. Br J Cancer 97:118–122CrossRefPubMedGoogle Scholar
  34. 34.
    Anderson LA, Watson RG, Murphy SJ et al (2007) Risk factors for Barrett’s oesophagus and oesophageal adenocarcinoma: results from the FINBAR study. World J Gastroenterol 13:1585–1594PubMedGoogle Scholar
  35. 35.
    Brown LM, Swanson CA, Gridley G et al (1995) Adenocarcinoma of the esophagus: role of obesity and diet. J Natl Cancer Inst 87:104–109CrossRefPubMedGoogle Scholar
  36. 36.
    Kubo A, Levin TR, Block G et al (2008) Dietary antioxidants, fruits, and vegetables and the risk of Barrett’s esophagus. Am J Gastroenterol 103:1614–1623CrossRefPubMedGoogle Scholar
  37. 37.
    Terry P, Lagergren J, Hansen H, Wolk A, Nyren O (2001) Fruit and vegetable consumption in the prevention of oesophageal and cardia cancers. Eur J Cancer Prev 10:365–369CrossRefPubMedGoogle Scholar
  38. 38.
    Kubo A, Levin TR, Block G et al (2008) Dietary patterns and the risk of Barrett’s esophagus. Am J Epidemiol 167:839–846CrossRefPubMedGoogle Scholar
  39. 39.
    Cross AJ, Leitzmann MF, Gail MH, Hollenbeck AR, Schatzkin A, Sinha R (2007) A prospective study of red and processed meat intake in relation to cancer risk. PLoS Med 4:e325CrossRefPubMedGoogle Scholar
  40. 40.
    Gonzalez CA, Jakszyn P, Pera G et al (2006) Meat intake and risk of stomach and esophageal adenocarcinoma within the European prospective investigation into cancer and nutrition (EPIC). J Natl Cancer Inst 98:345–354CrossRefPubMedGoogle Scholar
  41. 41.
    Navarro Silvera SA, Mayne ST, Risch H et al (2008) Food group intake and risk of subtypes of esophageal and gastric cancer. Int J Cancer 123:852–860CrossRefPubMedGoogle Scholar
  42. 42.
    Lagiou P, Talamini R, Samoli E et al (2001) Diet and upper-aerodigestive tract cancer in Europe: the ARCAGE study. Int J Cancer 124:2671–2676CrossRefGoogle Scholar
  43. 43.
    Mayne ST, Risch HA, Dubrow R et al (2001) Nutrient intake and risk of subtypes of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev 10:1055–1062PubMedGoogle Scholar
  44. 44.
    Chen H, Tucker KL, Graubard BI et al (2002) Nutrient intakes and adenocarcinoma of the esophagus and distal stomach. Nutr Cancer 42:33–40CrossRefPubMedGoogle Scholar
  45. 45.
    Hughes R, Cross AJ, Pollock JR, Bingham S (2001) Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation. Carcinogenesis 22:199–202CrossRefPubMedGoogle Scholar
  46. 46.
    Lin K, Shen W, Shen Z, Wu Y, Lu S (2002) Dietary exposure and urinary excretion of total N-nitroso compounds, nitrosamino acids and volatile nitrosamine in inhabitants of high- and low-risk areas for esophageal cancer in southern China. Int J Cancer 102:207–211CrossRefPubMedGoogle Scholar
  47. 47.
    Schaefer EJ, Augustin JL, Schaefer MM et al (2000) Lack of efficacy of a food-frequency questionnaire in assessing dietary macronutrient intakes in subjects consuming diets of known composition. Am J Clin Nutr 71:746–751PubMedGoogle Scholar
  48. 48.
    Beutler E, Felitti V, Ho NJ, Gelbart T (2002) Relationship of body iron stores to levels of serum ferritin, serum iron, unsaturated iron binding capacity and transferrin saturation in patients with iron storage disease. Acta Hemeatol 107:145–149CrossRefGoogle Scholar
  49. 49.
    Mei Z, Cogswell ME, Parvanta I et al (2005) Hemoglobin and ferritin are currently the most efficient indicators of population response to iron interventions: an analysis of nine randomized controlled trials. J Nutr 135:1974–1980PubMedGoogle Scholar
  50. 50.
    Longnecker MP, Stram DO, Taylor PR et al (1996) Use of selenium concentration in whole blood, serum, toenails, or urine as a surrogate measure of selenium intake. Epidemiology 7:384–390CrossRefPubMedGoogle Scholar
  51. 51.
    Fleming DJ, Jacques PF, Dallal GE, Tucker KL, Wilson PW, Wood RJ (1998) Dietary determinants of iron stores in a free-living elderly population: the Framingham heart study. Am J Clin Nutr 67:722–733PubMedGoogle Scholar
  52. 52.
    Cook JD, Reddy MB (2001) Effect of ascorbic acid intake on nonheme-iron absorption from a complete diet. Am J Clin Nutr 73:93–98PubMedGoogle Scholar
  53. 53.
    Diaz M, Rosado JL, Allen LH, Abrams S, Garcia OP (2003) The efficacy of a local ascorbic acid-rich food in improving iron absorption from Mexican diets: a field study using stable isotopes. Am J Clin Nutr 78:436–440PubMedGoogle Scholar
  54. 54.
    Cook JD, Noble NL, Morck TA, Lynch SR, Petersburg SJ (1983) Effect of fiber on nonheme iron absorption. Gastroenterology 85:1354–1358PubMedGoogle Scholar
  55. 55.
    Cook JD (1997) Food iron availability: back to the basics. Am J Clin Nutr 67:593–594Google Scholar
  56. 56.
    Fleming DJ, Tucker KL, Jacques PF, Dallal GE, Wilson PW, Wood RJ (2002) Dietary factors associated with the risk of high iron stores in the elderly Framingham heart study cohort. Am J Clin Nutr 76:1375–1384PubMedGoogle Scholar
  57. 57.
    Hurrell RF (1997) Bioavailability of iron. Eur J Clin Nutr 51:S4–S8PubMedGoogle Scholar
  58. 58.
    Peneau S, Dauchet L, Vergnaud AC et al (2008) Relationship between iron status and dietary fruit and vegetables based on their vitamin C and fiber content. Am J Clin Nutr 87:1298–1305PubMedGoogle Scholar
  59. 59.
    Kubo A, Corley DA (2007) Meta-analysis of antioxidant intake and the risk of esophageal and gastric cardia adenocarcinoma. Am J Gastroenterol 102:2323–2330CrossRefPubMedGoogle Scholar
  60. 60.
    Tzonou A, Lipworth L, Garidou A et al (1996) Diet and risk of esophageal cancer by histologic type in a low-risk population. Int J Cancer 68:300–304CrossRefPubMedGoogle Scholar
  61. 61.
    Mulholland HG, Cantwell MM, Anderson LA et al (2009) Glycemic index, carbohydrate and fiber intakes and risk of reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma. Cancer Causes Control 20:279–288CrossRefPubMedGoogle Scholar
  62. 62.
    McColl KE (2009) Effect of proton pump inhibitors on vitamins and iron. Am J Gastroenterol 104:S5–S9CrossRefPubMedGoogle Scholar
  63. 63.
    El-Serag HB (2002) The epidemic of esophageal adenocarcinoma. Gastroenterol Clin North Am 31:421–440 viiiGoogle Scholar
  64. 64.
    Cook JD (1990) Adaptation in iron metabolism. Am J Clin Nutr 51:301–308PubMedGoogle Scholar
  65. 65.
    Islami F, Kamangar F (2008) Helicobacter pylori and esophageal cancer risk: a meta-analysis. Cancer Prev Res (Phila Pa) 1:329–338Google Scholar
  66. 66.
    Muhsen K, Cohen D (2008) Helicobacter pylori infection and iron stores: a systematic review and meta-analysis. Helicobacter 13:323–340CrossRefPubMedGoogle Scholar
  67. 67.
    Hannon EM, Kiely M, Harrington KE, Robson PJ, Strain JJ, Flynn A (2001) The North/South Ireland food consumption survey: mineral intakes in 18–64-year-old adults. Public Health Nutr 4:1081–1088CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Mark G. O’Doherty
    • 1
  • Christian C. Abnet
    • 2
  • Liam J. Murray
    • 1
  • Jayne V. Woodside
    • 3
  • Lesley A. Anderson
    • 1
  • John D. Brockman
    • 4
  • Marie M. Cantwell
    • 1
  1. 1.Cancer Epidemiology Health Services Research Group, Centre for Public HealthQueens University BelfastBelfastUK
  2. 2.Department of Health and Human ServicesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of HealthRockvilleUSA
  3. 3.Nutrition and Metabolism Group, Centre for Public HealthQueens University Belfast, Institute of Clinical Science BBelfastUK
  4. 4.Research Reactor CenterUniversity of Missouri-ColumbiaColumbiaUSA

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