Carcinogenesis‑related changes in iron metabolism in chronic obstructive pulmonary disease subjects with lung cancer

Brzóska,Kamil; Bartłomiejczyk,Teresa; Sochanowicz,Barbara; Cymerman,Magdalena; Grudny,Jacek; Kołakowski,Jacek; Kruszewski,Marcin; Śliwiński,Paweł; Roszkowski‑Śliż,Kazimierz; Kapka‑Skrzypczak,Lucyna

doi:10.3892/ol.2018.9459

Carcinogenesis‑related changes in iron metabolism in chronic obstructive pulmonary disease subjects with lung cancer

Authors:
- Kamil Brzóska
- Teresa Bartłomiejczyk
- Barbara Sochanowicz
- Magdalena Cymerman
- Jacek Grudny
- Jacek Kołakowski
- Marcin Kruszewski
- Paweł Śliwiński
- Kazimierz Roszkowski‑Śliż
- Lucyna Kapka‑Skrzypczak
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Affiliations: Institute of Nuclear Chemistry and Technology, Centre for Radiobiology and Biological Dosimetry, 03‑195 Warsaw, Poland, Institute of Tuberculosis and Lung Diseases, Third Department of Lung Diseases, 01‑138 Warsaw, Poland, Institute of Tuberculosis and Lung Diseases, Department of Diagnosis and Treatment of Respiratory Insufficiency, 01‑138 Warsaw, Poland, Institute of Rural Health, Department of Molecular Biology and Translational Research, 20‑090 Lublin, Poland
Published online on: September 19, 2018 https://doi.org/10.3892/ol.2018.9459
Pages: 6831-6837

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Abstract

Chronic obstructive pulmonary disease (COPD) is often accompanied by lung cancer. In our previous work, it was observed that matrix metalloproteinase‑3 and haptoglobin (HP) polymorphisms were potential markers of enhanced susceptibility to lung cancer development among male COPD subjects. Here, results are reported on blood serum levels of several proteins involved in iron metabolism, inflammation and the oxidative stress response compared between the same groups of subjects. The blood serum levels of tumor necrosis factor α (TNFα), transferrin, hepcidin, ferritin, soluble transferrin receptor and 8‑oxo‑2'‑deoxyguanosine were compared, as well as total iron‑binding capacity (TIBC) and ceruloplasmin ferroxidase activity in two groups of subjects: Male COPD patients (54 subjects) and male COPD patients diagnosed with lung cancer (53 subjects). Statistically significant differences were identified between the two groups in transferrin and TNFα levels, as well as in TIBC; all three parameters were lower in the group consisting of COPD patients diagnosed with lung cancer (P<0.01). It was also revealed that HP genotype 1/2 was concomitant with low transferrin blood level in subjects with COPD; this apparent dependence was absent in the COPD + cancer subjects. The results indicate a role of iron metabolism in the susceptibility to lung cancer in COPD‑affected subjects. They also emphasize the importance of individual capacity for an effective response to oxidative stress during the pathogenic process as HP is a plasma protein that binds free hemoglobin and its polymorphism results in proteins with altered hemoglobin‑binding capacity and different antioxidant and iron‑recycling functions.

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1	Coussens LM and Werb Z: Inflammation and cancer. Nature. 420:860–867. 2002. View Article : Google Scholar : PubMed/NCBI
2	Dik S, Scheepers PT and Godderis L: Effects of environmental stressors on histone modifications and their relevance to carcinogenesis: A systematic review. Crit Rev Toxicol. 42:491–500. 2012. View Article : Google Scholar : PubMed/NCBI
3	Edwards TM and Myers JP: Environmental exposures and gene regulation in disease etiology. Environ Health Perspect. 115:1264–1270. 2007. View Article : Google Scholar : PubMed/NCBI
4	Hursting SD and Berger NA: Energy balance, host-related factors, and cancer progression. J Clin Oncol. 28:4058–4065. 2010. View Article : Google Scholar : PubMed/NCBI
5	Hursting SD and Hursting MJ: Growth signals, inflammation, and vascular perturbations: Mechanistic links between obesity, metabolic syndrome, and cancer. Arterioscler Thromb Vasc Biol. 32:1766–1770. 2012. View Article : Google Scholar : PubMed/NCBI
6	Maynard S, Schurman SH, Harboe C, de Souza-Pinto NC and Bohr VA: Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis. 30:2–10. 2009. View Article : Google Scholar : PubMed/NCBI
7	Weidman JR, Dolinoy DC, Murphy SK and Jirtle RL: Cancer susceptibility: Epigenetic manifestation of environmental exposures. Cancer J. 13:9–16. 2007. View Article : Google Scholar : PubMed/NCBI
8	Adcock IM, Caramori G and Barnes PJ: Chronic obstructive pulmonary disease and lung cancer: New molecular insights. Respiration. 81:265–284. 2011. View Article : Google Scholar : PubMed/NCBI
9	Decramer M, Janssens W and Miravitlles M: Chronic obstructive pulmonary disease. Lancet. 379:1341–1351. 2012. View Article : Google Scholar : PubMed/NCBI
10	Decramer M, Rennard S, Troosters T, Mapel DW, Giardino N, Mannino D, Wouters E, Sethi S and Cooper CB: COPD as a lung disease with systemic consequences-clinical impact, mechanisms, and potential for early intervention. COPD. 5:235–256. 2008. View Article : Google Scholar : PubMed/NCBI
11	Yang IA, Relan V, Wright CM, Davidson MR, Sriram KB, Francis Savarimuthu SM, Clarke BE, Duhig EE, Bowman RV and Fong KM: Common pathogenic mechanisms and pathways in the development of COPD and lung cancer. Expert Opin Ther Targets. 15:439–456. 2011. View Article : Google Scholar : PubMed/NCBI
12	Young RP and Hopkins RJ: How the genetics of lung cancer may overlap with COPD. Respirology. 16:1047–1055. 2011. View Article : Google Scholar : PubMed/NCBI
13	Bozinovski S, Vlahos R, Anthony D, McQualter J, Anderson G, Irving L and Steinfort D: COPD and squamous cell lung cancer: Aberrant inflammation and immunity is the common link. Br J Pharmacol. 173:635–648. 2016. View Article : Google Scholar : PubMed/NCBI
14	Durham AL and Adcock IM: The relationship between COPD and lung cancer. Lung Cancer. 90:121–127. 2015. View Article : Google Scholar : PubMed/NCBI
15	Aoshiba K, Zhou F, Tsuji T and Nagai A: DNA damage as a molecular link in the pathogenesis of COPD in smokers. Eur Respir J. 39:1368–1376. 2012. View Article : Google Scholar : PubMed/NCBI
16	Brzóska K, Bartlomiejczyk T, Sochanowicz B, Cymerman M, Grudny J, Kołakowski J, Kapka-Skrzypczak L, Kruszewski M, Sliwiński P and Roszkowski-Śliż K: Matrix metalloproteinase 3 polymorphisms as a potential marker of enhanced susceptibility to lung cancer in chronic obstructive pulmonary disease subjects. Ann Agric Environ Med. 21:546–551. 2014. View Article : Google Scholar : PubMed/NCBI
17	Grudny J, Kolakowski J, Kruszewski M, Szopiński J, Sliwiński P, Wiatr E, Winek J, Załęska J, Zych J and Roszkowski-Śliż K: Association of genetic dependences between lung cancer and chronic obstructive pulmonary disease. Pneumonol Alergol Pol. 81:308–318. 2013.PubMed/NCBI
18	Goldenstein H, Levy NS and Levy AP: Haptoglobin genotype and its role in determining heme-iron mediated vascular disease. Pharmacol Res. 66:1–6. 2012. View Article : Google Scholar : PubMed/NCBI
19	Kruszewski M: Labile iron pool: The main determinant of cellular response to oxidative stress. Mutat Res. 531:81–92. 2003. View Article : Google Scholar : PubMed/NCBI
20	Erel O: Automated measurement of serum ferroxidase activity. Clin Chem. 44:2313–2319. 1998.PubMed/NCBI
21	Boukhenouna S, Wilson MA, Bahmed K and Kosmider B: Reactive oxygen species in chronic obstructive pulmonary disease. Oxid Med Cell Longev. 2018:57303952018. View Article : Google Scholar : PubMed/NCBI
22	Markkanen E: Not breathing is not an option: How to deal with oxidative DNA damage. DNA Repair (Amst). 59:82–105. 2017. View Article : Google Scholar : PubMed/NCBI
23	Lewandowska H, Kalinowska M, Lewandowski W, Stepkowski TM and Brzóska K: The role of natural polyphenols in cell signaling and cytoprotection against cancer development. J Nutr Biochem. 32:1–19. 2016. View Article : Google Scholar : PubMed/NCBI
24	Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, Gargiulo G, Testa G, Cacciatore F, Bonaduce D and Abete P: Oxidative stress, aging, and diseases. Clin Interv Aging. 13:757–772. 2018. View Article : Google Scholar : PubMed/NCBI
25	Hung RJ, Hall J, Brennan P and Boffetta P: Genetic polymorphisms in the base excision repair pathway and cancer risk: A HuGE review. Am J Epidemiol. 162:925–942. 2005. View Article : Google Scholar : PubMed/NCBI
26	López-Cima MF, Gonzalez-Arriaga P, Garcia-Castro L, Pascual T, Marrón MG, Puente XS and Tardón A: Polymorphisms in XPC, XPD, XRCC1, and XRCC3 DNA repair genes and lung cancer risk in a population of northern Spain. BMC Cancer. 7:1622007. View Article : Google Scholar : PubMed/NCBI
27	Manuguerra M, Saletta F, Karagas MR, Berwick M, Veglia F, Vineis P and Matullo G: XRCC3 and XPD/ERCC2 single nucleotide polymorphisms and the risk of cancer: A HuGE review. Am J Epidemiol. 164:297–302. 2006. View Article : Google Scholar : PubMed/NCBI
28	Park JY, Lee SY, Jeon HS, Bae NC, Chae SC, Joo S, Kim CH, Park JH, Kam S, Kim IS and Jung TH: Polymorphism of the DNA repair gene XRCC1 and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev. 11:23–27. 2002.PubMed/NCBI
29	Zhou W, Liu G, Miller DP, Thurston SW, Xu LL, Wain JC, Lynch TJ, Su L and Christiani DC: Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk. Cancer Epidemiol Biomarkers Prev. 12:359–365. 2003.PubMed/NCBI
30	Hung RJ, Christiani DC, Risch A, Popanda O, Haugen A, Zienolddiny S, Benhamou S, Bouchardy C, Lan Q, Spitz MR, et al: International lung cancer consortium: Pooled analysis of sequence variants in DNA repair and cell cycle pathways. Cancer Epidemiol Biomarkers Prev. 17:3081–3089. 2008. View Article : Google Scholar : PubMed/NCBI
31	Dempsey E and Rudd PM: Acute phase glycoproteins: Bystanders or participants in carcinogenesis? Ann N Y Acad Sci. 1253:122–132. 2012. View Article : Google Scholar : PubMed/NCBI
32	Delanghe JR and Langlois MR: Haptoglobin polymorphism and body iron stores. Clin Chem Lab Med. 40:212–216. 2002. View Article : Google Scholar : PubMed/NCBI
33	Dobryszycka W: Biological functions of haptoglobin-new pieces to an old puzzle. Eur J Clin Chem Clin Biochem. 35:647–654. 1997.PubMed/NCBI
34	Nielsen MJ and Moestrup SK: Receptor targeting of hemoglobin mediated by the haptoglobins: Roles beyond heme scavenging. Blood. 114:764–771. 2009. View Article : Google Scholar : PubMed/NCBI
35	Levy AP, Asleh R, Blum S, Levy NS, Miller-Lotan R, Kalet-Litman S, Anbinder Y, Lache O, Nakhoul FM, Asaf R, et al: Haptoglobin: Basic and clinical aspects. Antioxid Redox Signal. 12:293–304. 2010. View Article : Google Scholar : PubMed/NCBI
36	Sadrzadeh SM and Bozorgmehr J: Haptoglobin phenotypes in health and disorders. Am J Clin Pathol. 121 Suppl:S97–S104. 2004.PubMed/NCBI
37	Wassell J: Haptoglobin: Function and polymorphism. Clin Lab. 46:547–552. 2000.PubMed/NCBI
38	Huang X: Iron overload and its association with cancer risk in humans: Evidence for iron as a carcinogenic metal. Mutat Res. 533:153–171. 2003. View Article : Google Scholar : PubMed/NCBI
39	Knekt P, Reunanen A, Takkunen H, Aromaa A, Heliövaara M and Hakulinen T: Body iron stores and risk of cancer. Int J Cancer. 56:379–382. 1994. View Article : Google Scholar : PubMed/NCBI
40	Selby JV and Friedman GD: Epidemiologic evidence of an association between body iron stores and risk of cancer. Int J Cancer. 41:677–682. 1988. View Article : Google Scholar : PubMed/NCBI
41	Toyokuni S and Sagripanti JL: Association between 8-hydroxy-2′-deoxyguanosine formation and DNA strand breaks mediated by copper and iron. Free Radic Biol Med. 20:859–864. 1996. View Article : Google Scholar : PubMed/NCBI
42	Zhou W, Park S, Liu G, Miller DP, Wang LI, Pothier L, Wain JC, Lynch TJ, Giovannucci E and Christiani DC: Dietary iron, zinc, and calcium and the risk of lung cancer. Epidemiology. 16:772–779. 2005. View Article : Google Scholar : PubMed/NCBI
43	Richardson DR, Kalinowski DS, Lau S, Jansson PJ and Lovejoy DB: Cancer cell iron metabolism and the development of potent iron chelators as anti-tumour agents. Biochim Biophys Acta. 1790:702–717. 2009. View Article : Google Scholar : PubMed/NCBI
44	Wang SJ, Gao C and Chen BA: Advancement of the study on iron metabolism and regulation in tumor cells. Chin J Cancer. 29:451–455. 2010. View Article : Google Scholar : PubMed/NCBI