Cancer Causes & Control

, Volume 24, Issue 6, pp 1175–1183 | Cite as

Intakes of heme iron and zinc and colorectal cancer incidence: a meta-analysis of prospective studies

  • Lei Qiao
  • Yong FengEmail author
Original paper



Epidemiologic findings concerning the associations between intakes of heme iron and zinc and colorectal cancer (CRC) incidence yielded conflicting results. We aimed to investigate the associations by performing a meta-analysis of prospective studies.


We conducted a literature search on PubMed and EMBASE databases up to December 2012 to identify the prospective studies that investigated the relationships between heme iron or zinc intake and risk of CRC. We also reviewed the bibliographies of the retrieved articles to identify additional studies. We used a random-effects model to calculate the summary relative risks (RRs) with 95 % confidence intervals (CIs).


Eight studies on heme iron intake and six studies on zinc intake met the inclusion criteria. The summary RR of CRC for the highest versus the lowest intake was 1.14 (95 % CI = 1.04–1.24) for heme iron and 0.83 (95 % CI = 0.72–0.94) for zinc, respectively. The observed associations were not significantly modified by subsites within the colorectum, sex, geographic area, study duration, the number of cases, or the range of intakes. In the dose–response analyses, the summary RR of CRC was 1.11 (95 % CI = 1.03–1.18) for heme iron intake of 1 mg/day, and 0.86 (95 % CI = 0.78–0.96) for zinc intake of 5 mg/day, respectively. There was little evidence of publication bias.


This meta-analysis suggests a significant positive dose–response association of heme iron intake and a significant inverse dose–response association of zinc intake with risk of CRC.


Heme iron Zinc Cohort studies Colorectal cancer Meta-analysis 


Conflict of interest

The authors declare no conflict of interest.


  1. 1.
    Chan DS, Lau R, Aune D, Vieira R, Greenwood DC, Kampman E, Norat T (2011) Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies. PLoS ONE 6:e20456PubMedCrossRefGoogle Scholar
  2. 2.
    Lakshmi VM, Clapper ML, Chang WC, Zenser TV (2005) Hemin potentiates nitric oxide-mediated nitrosation of 2-amino-3-methylimidazo [4, 5-f]quinoline (IQ) to 2-nitrosoamino-3-methylimidazo [4, 5-f] quinoline. Chem Res Toxicol 18:528–535PubMedCrossRefGoogle Scholar
  3. 3.
    Lakshmi VM, Nauseef WM, Zenser TV (2005) Myeloperoxidase potentiates nitric oxide-mediated nitrosation. J Biol Chem 280:1746–1753PubMedCrossRefGoogle Scholar
  4. 4.
    Cross AJ, Pollock JR, Bingham SA (2003) Haem, not protein or inorganic iron, is responsible for endogenous intestinal N-nitrosation arising from red meat. Cancer Res 63:2358–2360PubMedGoogle Scholar
  5. 5.
    Huang X (2003) Iron overload and its association with cancer risk in humans: evidence for iron as a carcinogenic metal. Mutat Res 533:153–171PubMedCrossRefGoogle Scholar
  6. 6.
    Nelson RL (1992) Dietary iron and colorectal cancer risk. Free Radic Biol Med 12:161–168PubMedCrossRefGoogle Scholar
  7. 7.
    Toyokuni S (1996) Iron-induced carcinogenesis: the role of redox regulation. Free Radic Biol Med 20:553–566PubMedCrossRefGoogle Scholar
  8. 8.
    Bastide NM, Pierre FH, Corpet DE (2011) Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved. Cancer Prev Res (Phila) 4:177–184CrossRefGoogle Scholar
  9. 9.
    Cross AJ, Ferrucci LM, Risch A, Graubard BI, Ward MH, Park Y, Hollenbeck AR, Schatzkin A, Sinha R (2010) A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association. Cancer Res 70:2406–2414PubMedCrossRefGoogle Scholar
  10. 10.
    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 96:403–407PubMedCrossRefGoogle Scholar
  11. 11.
    Hara A, Sasazuki S, Inoue M, Iwasaki M, Shimazu T, Sawada N, Yamaji T, Takachi R, Tsugane S (2012) Zinc and heme iron intakes and risk of colorectal cancer: a population-based prospective cohort study in Japan. Am J Clin Nutr 96:864–873PubMedCrossRefGoogle Scholar
  12. 12.
    Zhang X, Giovannucci EL, Smith-Warner SA, Wu K, Fuchs CS, Pollak M, Willett WC, Ma J (2011) A prospective study of intakes of zinc and heme iron and colorectal cancer risk in men and women. Cancer Causes Control 22:1627–1637PubMedCrossRefGoogle Scholar
  13. 13.
    Hansen RD, Albieri V, Tjonneland A, Overvad K, Andersen KK, Raaschou-Nielsen O (2012) Effects of smoking and antioxidant micronutrients on risk of colorectal cancer. Clin Gastroenterol HepatolGoogle Scholar
  14. 14.
    Larsson SC, Adami HO, Giovannucci E, Wolk A (2005) Re: Heme iron, zinc, alcohol consumption, and risk of colon cancer. J Natl Cancer Inst 97:232–233PubMedCrossRefGoogle Scholar
  15. 15.
    Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283:2008–2012PubMedCrossRefGoogle Scholar
  16. 16.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  17. 17.
    Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose–response data, with applications to meta-analysis. Am J Epidemiol 135:1301–1309PubMedGoogle Scholar
  18. 18.
    Balder HF, Vogel J, Jansen MC, Weijenberg MP, van den Brandt PA, Westenbrink S, van der Meer R, Goldbohm RA (2006) Heme and chlorophyll intake and risk of colorectal cancer in the Netherlands cohort study. Cancer Epidemiol Biomarkers Prev 15:717–725PubMedCrossRefGoogle Scholar
  19. 19.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558PubMedCrossRefGoogle Scholar
  20. 20.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedCrossRefGoogle Scholar
  21. 21.
    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 97:118–122PubMedCrossRefGoogle Scholar
  22. 22.
    Sesink AL, Termont DS, Kleibeuker JH, Van der Meer R (1999) Red meat and colon cancer: the cytotoxic and hyperproliferative effects of dietary heme. Cancer Res 59:5704–5709PubMedGoogle Scholar
  23. 23.
    Sesink AL, Termont DS, Kleibeuker JH, Van Der Meer R (2000) Red meat and colon cancer: dietary haem, but not fat, has cytotoxic and hyperproliferative effects on rat colonic epithelium. Carcinogenesis 21:1909–1915PubMedCrossRefGoogle Scholar
  24. 24.
    Pierre F, Freeman A, Tache S, Van der Meer R, Corpet DE (2004) Beef meat and blood sausage promote the formation of azoxymethane-induced mucin-depleted foci and aberrant crypt foci in rat colons. J Nutr 134:2711–2716PubMedGoogle Scholar
  25. 25.
    Dhawan DK, Chadha VD (2010) Zinc: a promising agent in dietary chemoprevention of cancer. Indian J Med Res 132:676–682PubMedGoogle Scholar
  26. 26.
    Simon SF, Taylor CG (2001) Dietary zinc supplementation attenuates hyperglycemia in db/db mice. Exp Biol Med (Maywood) 226:43–51Google Scholar
  27. 27.
    Marreiro DN, Geloneze B, Tambascia MA, Lerario AC, Halpern A, Cozzolino SM (2006) Effect of zinc supplementation on serum leptin levels and insulin resistance of obese women. Biol Trace Elem Res 112:109–118PubMedCrossRefGoogle Scholar
  28. 28.
    Chadha VD, Goel A, Dhawan D (2011) Regulatory role of zinc on the biokinetics and biodistribution of (65)Zn during the initiation of experimentally induced colon cancer. Nutr Cancer 63:212–217PubMedCrossRefGoogle Scholar
  29. 29.
    Zhao Z, Li S, Liu G, Yan F, Ma X, Huang Z, Tian H (2012) Body iron stores and heme-iron intake in relation to risk of type 2 diabetes: a systematic review and meta-analysis. PLoS ONE 7:e41641PubMedCrossRefGoogle Scholar
  30. 30.
    Sun Q, van Dam RM, Willett WC, Hu FB (2009) Prospective study of zinc intake and risk of type 2 diabetes in women. Diabetes Care 32:629–634PubMedCrossRefGoogle Scholar
  31. 31.
    Luo W, Cao Y, Liao C, Gao F (2012) Diabetes mellitus and the incidence and mortality of colorectal cancer: a meta-analysis of twenty four cohort studies. Colorectal Dis 14:1307–1312Google Scholar
  32. 32.
    Sesink AL, Termont DS, Kleibeuker JH, Van der Meer R (2001) Red meat and colon cancer: dietary haem-induced colonic cytotoxicity and epithelial hyperproliferation are inhibited by calcium. Carcinogenesis 22:1653–1659PubMedCrossRefGoogle Scholar
  33. 33.
    Pierre F, Tache S, Petit CR, Van der Meer R, Corpet DE (2003) Meat and cancer: haemoglobin and haemin in a low-calcium diet promote colorectal carcinogenesis at the aberrant crypt stage in rats. Carcinogenesis 24:1683–1690PubMedCrossRefGoogle Scholar
  34. 34.
    Pierre F, Santarelli R, Tache S, Gueraud F, Corpet DE (2008) Beef meat promotion of dimethylhydrazine-induced colorectal carcinogenesis biomarkers is suppressed by dietary calcium. Br J Nutr 99:1000–1006PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Colorectal Surgery and OncologyShengjing Hospital of China Medical UniversityShenyangChina

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