Skip to main content

Advertisement

Springer Nature Link
Log in

Plasma ferritin levels, HFE polymorphisms, and risk of pancreatic cancer among Chinese Han population

  • Research Article
  • Published:
Tumor Biology

Abstract

The etiology of pancreatic cancer (PC) remains poorly understood. High iron levels can increase the formation of noxious oxygen radicals, which are thought to promote carcinogenesis. The aim of this study was to determine whether iron biomarkers and HFE genotypes, which influence iron regulation, constitute risk factors for PC. A case–control study was conducted to examine plasma ferritin levels (n = 1,000 cases; 1,004 controls), two hemochromatosis gene (HFE) SNPs (n = 1,386 cases; 1,386 controls), and PC risk. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by unconditional logistic regression. We did not observe a significant association between plasma ferritin and PC risk. However, HFE rs1799945 was significantly associated with PC risk, with each additional copy of minor allele T being associated with a 1.21-fold increased risk of PC (OR = 1.21, 95 % CI 1.05–1.39, P = 7.72 × 10−3). Overall, high iron levels do not increase the risk of PC. Our observation that HFE rs1799945 increased PC risk warrants replication in additional study populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hariharan D, Saied A, Kocher HM. Analysis of mortality rates for pancreatic cancer across the world. HPB: Off J Int Hepato Pancreato Biliary Assoc. 2008;10:58–62.

    Article  CAS  Google Scholar 

  2. Chen H, Zhou B, Lan X, Wei D, Yuan T, Chen P. Association between single-nucleotide polymorphisms of OGG1 gene and pancreatic cancer risk in Chinese Han population. Tumour Biol. 2014;35:809–13.

    Article  CAS  PubMed  Google Scholar 

  3. Toyokuni S. Iron-induced carcinogenesis: the role of redox regulation. Free Radic Biol Med. 1996;20:553–66.

    Article  CAS  PubMed  Google Scholar 

  4. Richmond HG. Induction of sarcoma in the rat by iron–dextran complex. Br Med J. 1959;1:947–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Huang X. Iron overload and its association with cancer risk in humans: evidence for iron as a carcinogenic metal. Mutat Res. 2003;533:153–71.

    Article  CAS  PubMed  Google Scholar 

  6. Nelson RL, Davis FG, Sutter E, Sobin LH, Kikendall JW, Bowen P. Body iron stores and risk of colonic neoplasia. J Natl Cancer Inst. 1994;86:455–60.

    Article  CAS  PubMed  Google Scholar 

  7. Stevens RG, Morris JE, Cordis GA, Anderson LE, Rosenberg DW, Sasser LB. Oxidative damage in colon and mammary tissue of the HFE-knockout mouse. Free Radic Biol Med. 2003;34:1212–6.

    Article  CAS  PubMed  Google Scholar 

  8. Ruder EH, Berndt SI, Gilsing AM, Graubard BI, Burdett L, Hayes RB, Weissfeld JL, Ferrucci LM, Sinha R, Cross AJ. Dietary iron, iron homeostatic gene polymorphisms and the risk of advanced colorectal adenoma and cancer. Carcinogenesis 2014

  9. Krais A, Wortmann L, Hermanns L, Feliu N, Vahter M, Stucky S, Mathur S, Fadeel B. Targeted uptake of folic acid-functionalized iron oxide nanoparticles by ovarian cancer cells in the presence but not in the absence of serum. Nanomedicine: nanotechnology, biology, and medicine 2014.

  10. Marques O, da Silva BM, Porto G, Lopes C. Iron homeostasis in breast cancer. Cancer Lett 2014.

  11. Fonseca-Nunes A, Jakszyn P, Agudo A. Iron and cancer risk—a systematic review and meta-analysis of the epidemiological evidence. Cancer Epidemiol Biomarkers Prev. 2014;23:12–31.

    Article  CAS  PubMed  Google Scholar 

  12. Gilsing AM, Fransen F, de Kok TM, Goldbohm AR, Schouten LJ, de Bruine AP, et al. Dietary heme iron and the risk of colorectal cancer with specific mutations in KRAS and APC. Carcinogenesis. 2013;34:2757–66.

    Article  CAS  PubMed  Google Scholar 

  13. Ashmore JH, Lesko SM, Miller PE, Cross AJ, Muscat JE, Zhu J, et al. Association of dietary and supplemental iron and colorectal cancer in a population-based study. Eur J Cancer Prev. 2013;22:506–11.

    Article  CAS  PubMed  Google Scholar 

  14. Molina-Montes E, Wark PA, Sanchez MJ, Norat T, Jakszyn P, Lujan-Barroso L, et al. Dietary intake of iron, heme-iron and magnesium and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort. Int J Cancer. 2012;131:E1134–47.

    Article  CAS  PubMed  Google Scholar 

  15. Orlandi R, De Bortoli M, Ciniselli CM, Vaghi E, Caccia D, Garrisi V, et al. Hepcidin and ferritin blood level as noninvasive tools for predicting breast cancer. Ann Oncol. 2014;25:352–7.

    Article  CAS  PubMed  Google Scholar 

  16. Graff RE, Cho E, Lindstrom S, Kraft P, Willett WC, Eliassen AH. Premenopausal plasma ferritin levels, HFE polymorphisms, and risk of breast cancer in the Nurses’ Health Study II. Cancer Epidemiol Biomarkers Prev 2014.

  17. Hucl T, Kylanpaa-Back ML, Witt H, Kunzli B, Lempinen M, Schneider A, et al. HFE genotypes in patients with chronic pancreatitis and pancreatic adenocarcinoma. Genet Med. 2007;9:479–83.

    Article  PubMed  Google Scholar 

  18. Rossiello R, Carriero MV, Giordano GG. Distribution of ferritin, transferrin and lactoferrin in breast carcinoma tissue. J Clin Pathol. 1984;37:51–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Missmer SA, Smith-Warner SA, Spiegelman D, Yaun SS, Adami HO, Beeson WL, et al. Meat and dairy food consumption and breast cancer: a pooled analysis of cohort studies. Int J Epidemiol. 2002;31:78–85.

    Article  PubMed  Google Scholar 

  20. Ekblom K, Marklund SL, Palmqvist R, Van Guelpen B, Hallmans G, Weinehall L, et al. Iron biomarkers in plasma, HFE genotypes, and the risk for colorectal cancer in a prospective setting. Dis Colon Rectum. 2012;55:337–44.

    Article  PubMed  Google Scholar 

  21. Turedi A, Oymak Y, Mese T, Yaman Y, Bayraktaroglu S, Alpman A, et al. The effect of HFE polymorphisms on cardiac iron overload in patients with beta-thalassemia major. Pediatr Hematol Oncol. 2013;30:755–60.

    Article  CAS  PubMed  Google Scholar 

  22. Adams PC, McLaren CE, Speechley M, McLaren GD, Barton JC, Eckfeldt JH. HFE mutations in Caucasian participants of the Hemochromatosis and Iron Overload Screening Study with serum ferritin level <1000 microg/l. Can J Gastroenterol. 2013;27:390–2.

    PubMed Central  PubMed  Google Scholar 

  23. Galesloot TE, Geurts-Moespot AJ, den Heijer M, Sweep FC, Fleming RE, Kiemeney LA, et al. Associations of common variants in HFE and TMPRSS6 with iron parameters are independent of serum hepcidin in a general population: a replication study. J Med Genet. 2013;50:593–8.

    Article  CAS  PubMed  Google Scholar 

  24. Costa-Matos L, Batista P, Monteiro N, Henriques P, Girao F, Carvalho A. Hfe mutations and iron overload in patients with alcoholic liver disease. Arq Gastroenterol. 2013;50:35–41.

    PubMed  Google Scholar 

  25. Nandar W, Neely EB, Unger E, Connor JR. A mutation in the HFE gene is associated with altered brain iron profiles and increased oxidative stress in mice. Biochim Biophys Acta. 1832;2013:729–41.

    Google Scholar 

  26. Ali-Rahmani F, Huang MA, Schengrund CL, Connor JR, Lee SY. C282Y-HFE gene variant affects cholesterol metabolism in human neuroblastoma cells. PLoS ONE. 2014;9:e88724.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Liu X, Lv C, Luan X, Lv M. C282Y polymorphism in the HFE gene is associated with risk of breast cancer. Tumour Biol. 2013;34:2759–64.

    Article  CAS  PubMed  Google Scholar 

  28. Chen W, Zhao H, Li T, Yao H. HFE gene C282Y variant is associated with colorectal cancer in Caucasians: a meta-analysis. Tumour Biol. 2013;34:2255–9.

    Article  CAS  PubMed  Google Scholar 

  29. Ali-Rahmani F, Grigson PS, Lee S, Neely E, Connor JR, Schengrund CL. H63D mutation in hemochromatosis alters cholesterol metabolism and induces memory impairment. Neurobiol Aging 2013.

  30. Saliou P, Le Gac G, Mercier AY, Chanu B, Gueguen P, Merour MC, et al. Evidence for the high importance of co-morbid factors in HFE C282Y/H63D patients cared by phlebotomies: results from an observational prospective study. PLoS ONE. 2013;8:e81128.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Su XW, Lee SY, Mitchell RM, Stephens HE, Simmons Z, Connor JR. H63D HFE polymorphisms are associated with increased disease duration and decreased muscle superoxide dismutase-1 expression in amyotrophic lateral sclerosis patients. Muscle Nerve. 2013;48:242–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank all staff who were involved in the subject recruitment, telephone interviews, sample preparation, and laboratory assays for their hard works.

Conflict of interest

None

Author information

Authors and Affiliations

  1. Department of Surgical Oncology, Chinese PLA General Hospital, 100853, Beijing, China

    Zhiming Zhao, Chenggang Li, Minggeng Hu, Jidong Li & Rong Liu

Authors
  1. Zhiming Zhao
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Chenggang Li
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Minggeng Hu
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Jidong Li
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Rong Liu
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding authors

Correspondence to Zhiming Zhao or Rong Liu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, Z., Li, C., Hu, M. et al. Plasma ferritin levels, HFE polymorphisms, and risk of pancreatic cancer among Chinese Han population. Tumor Biol. 35, 7629–7633 (2014). https://doi.org/10.1007/s13277-014-1978-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-1978-x

Keywords