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

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Abstract

Background

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.

Methods

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).

Results

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.

Conclusion

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.

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References

  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:e20456

    Article  PubMed  CAS  Google Scholar 

  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 18:528–535

    Article  PubMed  CAS  Google Scholar 

  3. Lakshmi VM, Nauseef WM, Zenser TV (2005) Myeloperoxidase potentiates nitric oxide-mediated nitrosation. J Biol Chem 280:1746–1753

    Article  PubMed  CAS  Google Scholar 

  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 63:2358–2360

    PubMed  CAS  Google Scholar 

  5. Huang X (2003) Iron overload and its association with cancer risk in humans: evidence for iron as a carcinogenic metal. Mutat Res 533:153–171

    Article  PubMed  CAS  Google Scholar 

  6. Nelson RL (1992) Dietary iron and colorectal cancer risk. Free Radic Biol Med 12:161–168

    Article  PubMed  CAS  Google Scholar 

  7. Toyokuni S (1996) Iron-induced carcinogenesis: the role of redox regulation. Free Radic Biol Med 20:553–566

    Article  PubMed  CAS  Google Scholar 

  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) 4:177–184

    Article  CAS  Google Scholar 

  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 70:2406–2414

    Article  PubMed  CAS  Google Scholar 

  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 96:403–407

    Article  PubMed  CAS  Google Scholar 

  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 96:864–873

    Article  PubMed  CAS  Google Scholar 

  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 22:1627–1637

    Article  PubMed  Google Scholar 

  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 Hepatol

  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 97:232–233

    Article  PubMed  CAS  Google Scholar 

  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 283:2008–2012

    Article  PubMed  CAS  Google Scholar 

  16. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  17. Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose–response data, with applications to meta-analysis. Am J Epidemiol 135:1301–1309

    PubMed  CAS  Google Scholar 

  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 15:717–725

    Article  PubMed  CAS  Google Scholar 

  19. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  20. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  PubMed  CAS  Google Scholar 

  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 97:118–122

    Article  PubMed  CAS  Google Scholar 

  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 59:5704–5709

    PubMed  CAS  Google Scholar 

  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 21:1909–1915

    Article  PubMed  CAS  Google Scholar 

  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 134:2711–2716

    PubMed  CAS  Google Scholar 

  25. Dhawan DK, Chadha VD (2010) Zinc: a promising agent in dietary chemoprevention of cancer. Indian J Med Res 132:676–682

    PubMed  CAS  Google Scholar 

  26. Simon SF, Taylor CG (2001) Dietary zinc supplementation attenuates hyperglycemia in db/db mice. Exp Biol Med (Maywood) 226:43–51

    CAS  Google Scholar 

  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 112:109–118

    Article  PubMed  CAS  Google Scholar 

  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 63:212–217

    Article  PubMed  CAS  Google Scholar 

  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:e41641

    Article  PubMed  CAS  Google Scholar 

  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 32:629–634

    Article  PubMed  CAS  Google Scholar 

  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 14:1307–1312

    Google Scholar 

  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 22:1653–1659

    Article  PubMed  CAS  Google Scholar 

  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 24:1683–1690

    Article  PubMed  CAS  Google Scholar 

  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 99:1000–1006

    Article  PubMed  CAS  Google Scholar 

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Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Colorectal Surgery and Oncology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, China

    Lei Qiao & Yong Feng

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  1. Lei Qiao
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  2. Yong Feng
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Correspondence to Yong Feng.

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Qiao, L., Feng, Y. Intakes of heme iron and zinc and colorectal cancer incidence: a meta-analysis of prospective studies. Cancer Causes Control 24, 1175–1183 (2013). https://doi.org/10.1007/s10552-013-0197-x

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  • DOI: https://doi.org/10.1007/s10552-013-0197-x

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