Abstract
Lung cancer (LC) is the number one cancer killer of women both in the USA and around the world. Besides cigarette smoking, an important feature in the etiology of LC is its strong association with exposure of toxic metals. The primary objective of the present investigation was to assess the concentrations of toxic/essential elements (Ni, Ca, Se, Zn, Co, K, Cr, As, Cu, Na, Fe, Hg, Cd, Mg, Mn, and Pb) in the serum samples of LC female patients with female controls by atomic absorption spectrometry after wet-acid digestion procedure. Carcinoembryonic antigen (CEA) was also measured in the serum of the patients using immunoradiometric method. Comparative appraisal of the data revealed that concentrations of Cr, Mg, Cd, Pb, Hg, As, and Ni were noted to be high significantly in serum of LC female patients, while the average Fe, Co, Mn, Na, K, Zn, Ca, and Se were observed at higher levels in female controls (p < 0.05). The correlation study revealed significantly different mutual associations among the elements in the both donor groups. Markedly, variations in the elemental levels were also noted for different types (non-small cell lung cancer and small cell lung cancer) and stages (I, II, III, & IV) of LC patients. Multivariate analyses showed substantially diverse apportionment of the metals in the female patients and female controls. Hence, present findings suggest that the toxic and essential metals accumulated in the body may pose a high risk for LC progression in Pakistani females.
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Adams SV, Passarelli MN, Newcomb PA (2012) Cadmium exposure and cancer mortality in the third national health and nutrition examination survey cohort. Occup Environ Med 69(2):153–156
Callejon-Leblic B, Arias-Borrego A, Pereira-Vega A, Gomez-Ariza JL, Garcia-Barrera T (2019) The metallome of lung cancer and its potential use as biomarker. Int J Mol Sci 20:778
Zhang X, Yang Q (2018) Association between serum copper levels and lung cancer risk: a meta-analysis. J Int Med Res 46(12):4863–4873
Luqman M, Javed MM, Daud S, Raheem N, Ahmad J, Khan AH (2014) Risk factors for lung cancer in the Pakistani population. Asian Pac J Cancer Prev 15(7):3035–3039
Callejon-Leblic B, Gomez-Ariza JL, Pereira-Vega A, Garcia-Barrera T (2018) Metal dyshomeostasis based biomarkers of lung cancer using human biofluids. Metallomics 10:1444–1451
Person RJ, Ngalame NNO, Makia NL, Bell MW, Waalkes MP, Tokar EJ (2015) Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells. Toxicol Appl Pharmacol 286:36–43
Schnabel P, Junker K (2015) Pulmonary neuroendocrine tumors in the new WHO 2015 classification. Start of breaking new grounds? Pathologe 36:283–292
Zamay TN, Zamay GS, Kolovskaya OS, Zukov RA, Petrova MM, Gargaun A, Berezovski MV, Kichkailo AS (2017) Current and prospective protein biomarkers of lung cancer. Cancers 9:155
Vieira AR, Abar L, Vingeliene S, Chan DS, Aune D, Navarro-Rosenblatt D, Stevens C, Greenwood D, Norat T (2016) Fruits, vegetables and lung cancer risk: a systematic review and meta-analysis. Ann Oncol 27(1):81–96
North CM, Christiani DC (2013) Women and lung cancer: what is new? Semin Thoracic Surg 25:87–94
O'Keeffe LM, Taylor G, Huxley RR, Mitchell P, Peters SAE (2018) Smoking as a risk factor for lung cancer in women and men: a systematic review and meta-analysis. BMJ Open 8:e021611
Zablocka-Slowinska K, Placzkowska S, Prescha A, Pawelczyk K, Porębska I, Kosacka M, Pawlik-Sobecka L, Grajeta H (2018) Serum and whole blood Zn, Cu and Mn profiles and their relation to redox status in lung cancer patients. J Trace Elem Med Biol 45:78–84
Kligerman S, White C (2011) Epidemiology of lung cancer in women: risk factors, survival, and screening. Am J Roentgenol 196:287–295
Scimeca M, Ai O, Terrenato I, Bischetti S, Bonanno E (2014) Assessment of metal contaminants in non-small cell lung cancer by EDX microanalysis. Eur J Histochem 58(3):2403
Hanif S, Ilyas A, Shah MH (2018) Statistical evaluation of trace metals, TSH and T4 in blood serum of thyroid disease patients in comparison with controls. Biol Trace Elem Res 183(1):58–70
StatSoft (1999) STATISTICA for Windows. Computer Program Manual, StatSoft, Tusla
Jolliffe IT (2002) Principal component analysis, 2nd edn. Springer, New York
Sanikini H, Yuan JM, Butler LM, Koh WP, Gao UT, Steffen A, Johansson M, Vineis P, Goodman GE, Barnett MT, Hung RJ, Chen C, Stucker I (2018) Body mass index and lung cancer risk: a pooled analysis based on nested case control studies from four cohort studies. BMC Cancer 18:220
Duan P, Hu C, Quan C, Yi X, Zhou W, Yuan M, Yu T, Kourouma A, Yang K (2015) Body mass index and risk of lung cancer: systematic review and dose-response meta analysis. Sci Rep 5:16938
El-Zein M, Parent ME, Nicolau B, Koushik A, Siemiatycki J, Rousseau MC (2013) Body mass index, lifetime smoking intensity and lung cancer risk. Int J Cancer 133(7):1721–1731
Zhu H, Zhang S (2018) Body mass index and lung cancer risk in never smokers: a meta-analysis. BMC Cancer 18:635
Smith L, Brinton LA, Spitz MR, Lam TK, Park Y, Hollenbeck AR, Freedman ND, Gierach GL (2012) Body mass index and risk of lung cancer among never, former, and current smokers. J Natl Cancer Inst 104:778–789
Li X, Bai Y, Wang S, Nyamathira SM, Zhang X, Zhang W, Wang T, Deng Q, He M, Zhang X, Wu T, Guo H (2015) Association of body mass index with chromosome damage levels and lung cancer risk among males. Sci Rep 5:9458
Wang Y, Sun Z, Li A, Zhang Y (2019) Association between serum zinc levels and lung cancer: a meta-analysis of observational studies. World J Surg Oncol 17:78
Filaire E, Dupuis C, Galvaing G, Aubreton S, Laurent H, Richard R, Filaire M (2013) Lung cancer: what are the links with oxidative stress, physical activity and nutrition. Lung Cancer 82:383–389
Yang Y, Xu W, Yao Q, Qin L, Xu C (2016) Dairy product, calcium intake and lung cancer risk: a systematic review with meta-analysis. Sci Rep 6:20624
Skuladottir H, Tjoenneland A, Overvad K, Stripp C, Christensen J, Raaschou-Nielsen O, Olsen JH (2004) Does insufficient adjustment for smoking explain the preventive effects of fruit and vegetables on lung cancer? Lung Cancer 45(1):1–10
Buchner FL, Bueno-de-Mesquita HB, Linseisen J, Boshuizen HC, Kiemeney LA (2010) Fruits and vegetables consumption and the risk of histological subtypes of lung cancer in the European prospective investigation into cancer and nutrition (EPIC). Cancer Causes Control 21(3):357–371
Morissette MC, Lamontagne M, Berube JC, Gaschler G, Williams A (2014) Impact of cigarette smoke on the human and mouse lungs: a gene expression comparison study. PLoS One 9(3):e92498
Prasad S, Gupta SC, Pandey MK, Tyagi AK, Deb L (2016) Oxidative stress and cancer: advances and challenges. Oxidative Med Cell Longev 2016:5010423
Abdelgawad TT, Suliman LAE, Helaly AMN, Motawei SM, Abdelghanya DA (2018) Heavy metals assessment in Egyptian smokers with lung cancer. Egypt J Chest Dis Tuberc 67:56–61
Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283:65–87
Person RJ, Tokar EJ, Xu Y, Orihuela R, Ngalame NNO, Waalkes MP (2013) Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells. Toxicol Appl Pharmacol 273(2):281–288
Ciencewicki J, Trivedi S, Kleeberger S (2008) Oxidants and the pathogenesis of lung diseases. J Allergy Clin Immunol 122(3):456–468
Arita A, Costa M (2009) Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium. Metallomics 1:222–228
Koedrith P, Seo YR (2011) Advances in carcinogenic metal toxicity and potential molecular markers. Int J Mol Sci 12:9576–9595
NTP (2011) National Toxicology Program, 12th report on carcinogens, cadmium and cadmium compounds. Department of Health and Human Services, Research; Triangle Park, NC: 2011. p. 80–83
Lee DH, Jacobs DR Jr (2005) Interaction among heme iron, zinc, and supplemental vitamin c intake on the risk of lung cancer: Iowa women’s health study. Nutr Cancer 52(2):130–137
Gomez NN, Biaggio VS, Ciminari ME, Chaca MVP, Alvarez SM (2016) Zinc: what is your role in lung cancer? Nutr Defic. Chapter 3:47–53
Zowczak M, Iskra M, Paszkowski J, Manczak M, Torlinski L, Wysocka E (2001) Oxidase activity of ceruloplasmin and concentrations of copper and zinc in serum of cancer patients. J Trace Elem Med Biol 15(2–3):193–196
Bai Y, , Gege Wanga , Wenshan Fua , Yanjun Lub , Wei Weia , Weilin Chena , Xiulong Wua (2019) Circulating essential metals and lung cancer: risk assessment and potential molecular effects. Environ Int 127: 685–693
Gumulec J, Masarik M, Adam V, Eckschlager T, Provaznik I, Kizek R et al (2014) Serum and tissue zinc in epithelial malignancies: a meta-analysis. PLoS One 9:e99790
Singh N, Kumar A, Gupta VK, Sharma B (2018) Biochemical and molecular bases of lead-induced toxicity in mammalian systems and possible mitigations. Chem Res Toxicol 31:1009–1021
Garcia-Leston J, Mendez J, Pasaro E, Laffon B (2010) Genotoxic effects of lead: an updated review. Environ Int 36(6):623–636
Sukiennicki G, Muszynska M, Jaworska-Bieniek K, Kaczmarek K, Marciniak W, Lener M, Durda K, Gromowski T, Huzarski T, Byrski T, Gronwald J (2015) Iron as diagnostic marker of cancer. Hered Cancer in Clin Pract 13(2):A5
Al-Fartusie FS, Hafudh A, Mustafa N, Al-Bermani H, Majid AY (2017) Levels of some trace elements in sera of patients with lung cancer and in smokers. Indian J Adv Chem Sci 5(4):344–352
Lominadze D, Saari J, Percival S, Schuschke D (2004) Proinflammatory effects of copper deficiency on neutrophils and lung endothelial cells. Immunol Cell Biol 82:231–238
Proctor DM, Suh M, Campleman SL, Thompson CM (2014) Assessment of the mode of action for hexavalent chromium-induced lung cancer following inhalation exposures. Toxicology 325:160–179
Clementino M, Shi X, Zhang Z (2018) Oxidative stress and metabolic reprogramming in Cr(VI) carcinogenesis. Curr Opin Toxicol 8:20–27
ATSDR (2012) Toxicological profile for chromium. US Department of Health and Human Services, Public Health Service, Atlanta, GA
Sun HJ, Rathinasabapathi B, Wu B, Luo J, Pu LP, Ma LQ (2014) Arsenic and selenium toxicity and their interactive effects in humans. Environ Int 69:148–158
Smith AH, Marshall G, Liaw J, Yuan Y, Ferreccio C, Steinmaus C (2012) Mortality in young adults following in utero and childhood exposure to arsenic in drinking water. Environ Health Perspect 120(11):1527–1531
Garcia-Esquinas E, Pollan M, Usmans JG, Francesconi KA, Goessler W, Guallar E, Howard B, Farley J, Best LG, Navas-Acien A (2013) Arsenic exposure and cancer mortality in a US-based prospective cohort: the strong heart study. Cancer Epidemiol Biomark Prev 22(11):1944–1953
Nakadaira H, Endoh K, Katagiri M, Yamamoto M (2002) Elevated mortality from lung cancer associated with arsenic exposure for a limited duration. J Occup Environ Med 44(3):291–299
Demir N, Enon S, Turksoy VA, Kayaalti Z, Kaya S, Cangir AK, Soylemezoglu T, Savas I (2014) Association of cadmium but not arsenic levels in lung cancer tumor tissue with smoking, histopathological type and stage. Asian Pac J Cancer Prev 15(7):2965–2970
Clarkson TW, Magos L (2006) The toxicology of mercury and its chemical compounds. Crit Rev Toxicol 36:609–662
Luo J, Hendryx M, Ducatman A (2011) Association between six environmental chemicals and lung cancer incidence in the United States. J Environ Public Health 2011:463701
Jarup L (2003) Hazards of heavy metal contamination. Br Med Bull 68:167–182
Sadat A, Hossain MI, Hossain MK, Reza MS, Nahar Z, Islam SKN, Hasnat A (2008) Serum trace elements and immunoglobulin profile in lung cancer patients. J Appl Res 8(1):24–33
Amara S, Tiriveedhi V (2017) Inflammatory role of high salt level in tumor microenvironment (review). Int J Oncol 59:1477–1481
Peri A (2019) Prognostic and predictive role of hyponatremia in cancer patients. J Cancer Metastasis Treat 5:40
Fuca G, Galli G, Poggi M, Russo GL, Proto C, Imbimbo M, Vitali M et al (2018) Low baseline serum sodium concentration is associated with poor clinical outcomes in metastatic non-small cell lung cancer patients treated with immunotherapy. Target Oncol 13(6):795–800
Fiordoliva I, Meletani T, Baleani MG, Rinaldi S, Savini A, Paolo MDP, Berardi R (2017) Managing hyponatremia in lung cancer: latest evidence and clinical implications. Ther Adv Med Oncol 9(11):711–719
Chiou YH, Wong RH, Chao MR, Chen CY, Liou SH, Lee H (2014) Nickel accumulation in lung tissues is associated with increased risk of p53 mutation in lung cancer patients. Environ Mol Mutagen 55:624–632
Takata Y, Shu XO, Yang G, Li H, Dai Q, Gao J, Cai Q, Gao YT, Zheng W (2013) Calcium intake and lung cancer risk among female nonsmokers: a report from the Shanghai women's health study. Cancer Epidemiol Biomark Prev 22(1):50–57
Suh M, Thompson CM, Brorby GP, Mittal L, Proctor DM (2016) Inhalation cancer risk assessment of cobalt metal. Regul Toxicol Pharmacol 79:74–82
Lison D, Brule SV, Maele-Fabry GV (2018) Cobalt and its compounds: update on genotoxic and carcinogenic activities. Crit Rev Toxocol 48(7). https://doi.org/10.1080/10408444.2018.1491023
He FJ, MacGregor GA (2008) Beneficial effects of potassium on human health. Physiol Plant 133(4):725–735
Udensi KU, Tchounwou PB (2017) Potassium homeostasis, oxidative stress, and human disease. Int J Clin Exp Physiol 4(3):111–122
Song X, Zhong X, Tang K, Wu G, Jiang Y (2018) Serum magnesium levels and lung cancer risk: a meta-analysis. World J Surg Oncol 16(1):137
Wolf FI, Fedrica I, Trapani V, Cittadini A (2008) Magnesium and the control of cell proliferation: looking for a needle in a haystack. Magnes Res 21(2):83–91
Joshi G, Vyas RK, Gahlot G, Soni Y (2017) Altered level of serum magnesium in patients with esophageal and lung carcinoma. Int J Life Sci Scienti Res 3(4):1158–1161
Everitt BS, Landau S, Leese M, Stahl D (2011) Cluster analysis, 5th edn. Wiley, Chichester, UK
Acknowledgments
We would like to acknowledge the staff of the PINUM and Allied General Hospital, Faisalabad Medical University, Faisalabad, Pakistan, for their assistance during the study. Technical help by University of Education, Lahore, Pakistan, to execute this project is also acknowledged.
Funding
A. Irfan extends his appreciation to the Deanship of Scientific Research at King Khalid University, Saudi Arabia, for funding this work through research groups program under grant number R.G.P.2/44/40. In addition, the present study was supported by a Higher Education Commission, Islamabad, Pakistan, through Startup Research Grant Program 2018-19 (Project # 1955).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethical Review Committee, PINUM Faisalabad & Allied General Hospital, Faisalabad Medical University, Faisalabad REF. NO. UEFC/2018-S532 & UEFC/2018-S573 and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Qayyum, M.A., Farooq, Z., Yaseen, M. et al. Statistical Assessment of Toxic and Essential Metals in the Serum of Female Patients with Lung Carcinoma from Pakistan. Biol Trace Elem Res 197, 367–383 (2020). https://doi.org/10.1007/s12011-019-01998-8
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DOI: https://doi.org/10.1007/s12011-019-01998-8