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Table of Contents
ORIGINAL ARTICLE
Year : 2013  |  Volume : 12  |  Issue : 2  |  Page : 131-134  

Trace metals and total antioxidant potential in head and neck cancer patients


1 Department of Oral/Maxillofacial Surgery, College of Medicine, University of Ibadan, Oyo State, Nigeria
2 Department of Oral/Maxillofacial Surgery, College of Health sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria

Date of Web Publication22-May-2013

Correspondence Address:
V I Akinmoladun
Department of Oral/Maxillofacial Surgery, Faculty of Dentistry, College of Medicine, University of Ibadan, Ibadan, Oyo State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1596-3519.112411

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   Abstract 

Background/Objective: There are pieces of evidence suggesting that oxidative stress and immune responses play significant roles in the etiopathogenesis of some malignant diseases. Also increased oxidative stress in patients with certain cancer may result from changes in the levels of certain trace elements. Therefore antioxidants either in the form of trace metals or enzymes are important tools in the study of these conditions. This study aimed at measuring the level of oxidative stress in the head and neck cancer patients by using plasma total antioxidant potential and the plasma level of some antioxidant trace metals.
Materials and Methods: Twenty cases of head and neck squamous cell carcinoma recruited from the Oral and Maxillofacial surgery and Radiotherapy clinics of the University College Hospital, Ibadan were included in the study. While total antioxidant status was measured by ferric reducing antioxidant power (FRAP) assay of Benzie and Strain (1996), the plasma trace metals were assayed by atomic absorption spectrophotometry.
Result: The total antioxidant potential was significantly reduced in the study group when compared with controls. Zinc, iron, and selenium were also found to be significantly lower in the study group compared with controls.
Conclusion: The result suggests a state of oxidative stress in the head and neck cancer patients with likely impact on disease process and treatment outcome.

   Abstract in French 

Contexte/objectif: TVoici les éléments de preuve suggérant que le stress oxydatif et réponses immunitaires jouent un rôle important dans l'étiopathogénie de certaines maladies malignes. Aussi une augmentation de stress oxydatif chez les patients atteints de certain cancer peut résulter de changements dans les concentrations de certains oligo-éléments. C'est pourquoi les antioxydants sous forme de métaux-traces ou enzymes sont des outils importants dans l'étude de ces conditions. Cette étude visait à mesurer le niveau de stress oxydatif chez les patients atteints de cancer tête et cou en utilisant le potentiel d'antioxydant total plasmatique et le taux plasmatique de certains métaux-traces antioxydant.
Matériaux et méthodes: Vingt cas de carcinome épidermoïde cervicofaciale recrutement dans la chirurgie orale et maxillo-faciale et la radiothérapie cliniques de l'University College Hospital, Ibadan ont participé à l'étude. Alors que le statut antioxydant total a été mesurée par dosage réduction ferrique de puissance (PAF) antioxydant de Bertrand et souche (1996), les métaux traces de plasma ont été dosés par spectrophotométrie d'absorption atomique.
Résultat: Le potentiel d'antioxydant total a été significativement réduit dans le groupe d'étude par rapport aux témoins. Zinc, fer et sélénium se retrouvent également à être significativement plus faible dans le groupe d'étude comparé aux témoins.
Conclusion: Le résultat suggère un état de stress oxydatif chez les patients atteints de cancer tête et cou avec impact probable sur le résultat de processus et traitement de la maladie.
Mots clés: Tracer les métaux, le potentiel antioxydant total, tête cou

Keywords: Trace metals, total antioxidant potential, head neck cancer


How to cite this article:
Akinmoladun V I, Owotade F J, Olusanya A A. Trace metals and total antioxidant potential in head and neck cancer patients. Ann Afr Med 2013;12:131-4

How to cite this URL:
Akinmoladun V I, Owotade F J, Olusanya A A. Trace metals and total antioxidant potential in head and neck cancer patients. Ann Afr Med [serial online] 2013 [cited 2019 Dec 11];12:131-4. Available from: http://www.annalsafrmed.org/text.asp?2013/12/2/131/112411


   Introduction Top


Head and neck cancers include malignant tumors arising from a variety of sites in the upper aero-digestive tract. Analysis of these tumors reveals a heterogeneous neoplastic process involving numerous sites with unique sets of epidemiologic, pathologic, and treatment considerations. The most common histologic type is squamous cell carcinoma, which occurs in the oral cavity, oropharynx, hypopharynx, and larynx. Therefore, the term "head and neck squamous cell carcinoma" (HNSCC) is frequently used to imply squamous cell carcinomas involving these anatomical sites. [1]

Head and neck cancer, like other types of cancer, involves an interaction between carcinogens and the genes in a multistep fashion that eventually results in malignancy. Reactive oxygen species (ROS) have been implicated in many diseases particularly those of chronic course including cancers. [2],[3]

The body is equipped with antioxidants, including the enzymes superoxide dismutase, glutathione peroxidase, and catalase. Others are the antioxidant vitamins A, C, and E. These counteract the deleterious effects of reactive oxygen species, as they are constantly being produced during normal metabolic and physiological processes. [4],[5] The total antioxidant potential of the individual therefore is important, as it is a measure of the individual's ability to cope with or prevent a state of oxidative stress; a state of disequilibrium in which rate of generation of reactive oxygen species overwhelms the individual's ability to remove them. [6]

The importance of nutrients in the etiology of many cancers has recently gained wide acceptance. Diets containing "anticarcinogenic" substances such as carotenoids, vitamin C, and trace elements have been documented to have a role in the prevention of the carcinogenic process in experimental and animal model studies. [7],[8] Gowal, et al., [9] reported that a decline in the cell mediated immunity predisposes to oncogenesis, and a close association has been found between immune responses and macro- or micro-nutrient status. [10]

Trace elements have been studied in recent years to assess whether they have any modifying effect in the etiology of cancers since they are important in the maintenance of DNA integrity, [11],[12],[13] the results of such studies are however varied.


   Materials and Methods Top


Twenty consecutive, histologically diagnosed, and untreated cases of HNSCC who presented (within the study period and consented) at the Oral surgery and Radiotherapy clinics UCH, Ibadan were recruited for the study. They were aged between 20 and 73 years and made up of 14 males and 6 females. Twenty apparently healthy volunteers aged between 20 and 77 years and made up of 14 males and 6 females were also enrolled as control. The study was explained to the individuals and informed consents were obtained before samples were collected. Blood samples were collected in heparinized bottles and centrifuged in MSE centrifuge for 5 minutes at 3,500 rpm after which the plasma was separated into plain bottles and stored at -20°C until ready for assay of trace metals and total antioxidant potential.

Determination of plasma trace metals

Plasma levels of Cu, Mg, Fe, Zn, Mn, and Se were determined using atomic absorption spectrophotometer as previously described (Olaniyi and Arinola, 2007). [14]

Determination of total antioxidant potential

The plasma total antioxidant potential was determined by the FRAP (Ferrous Reducing Antioxidant Power) technique described by Benzie and Strain (1996).

Data analysis

The statistical analyses were done using SPSS ® version 17 for Windows. Descriptive statistics were determined and Mann-Whitney was used to compare mean values. The probability (P) equal or less than 0.05 was considered significant.


   Results Top


[Figure 1] shows sites distribution of lesions in the study group; the most frequently involved site in this study was the palatal mucosa, accounting for 8 (40%) of all recorded sites. The mean serum levels of Mg, Mn, and Cu were higher in HNSCC than the controls while those of Zn, Se, and Fe were lower in HNSCC compared with the controls. These values were statistically significant for Fe, Se, and Zn as illustrated in [Table 1]. The total antioxidant potential (TAP) in HNSCC was significantly lower than the values for the controls (P = 0.05).
Figure 1: Site distribution of cancers

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Table 1: The mean (±sd) serum levels of trace metals and total antioxidant potential between HNSCC and control

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   Discussion Top


Trace metals are important in the maintenance of the integrity of DNA; hence they have been extensively reported in malignancies. However the reports by various authors are not consistent for all cancer types and by various studies in same cancers. [11],[12],[14] Copper, zinc, selenium and other essential trace metals are components of enzymes. Variations in their serum levels may be important in the aetiopathogenesis of cancers. Raised levels of Cu had been reported in various malignant conditions. [15],[16] Silverman and Thompson [17] reported significant increases in Zinc and Copper levels in head and neck cancer patients. The reasons for this increase in serum copper levels among cancer patients are not known. It may result from increased liver production of copper-containing caeruloplasmin as an inflammatory response to the cancer (since increased Cu tends to accompany increased caeruloplasmin) or from a tumor-induced decrease in catabolism of the serum caeruloplasmin. [18],[19] Increased absorption from the gut, reduced urinary excretion, and cellular release by tumor during necrosis, are other probable reasons. Copper plays a major role in angiogenesis and by extension tumor proliferation, though the exact mechanism has not been fully elucidated. In this study, the mean serum concentrations of Cu, Mg, and Mn were higher in the HNSCC group than in the controls. The increases were however not statistically significant; P = 0.16, P = 0.17, P = 0.36 respectively.

Magnesium is a component of several enzymes; its role in cell cycle is also said to be central. Low serum levels of this metal in cancers, relative to controls, have been reported in the literature. [20],[21] This difference may be due to increased demand by the tumor cells since Mg is required for growth and cell division. There was a higher mean serum level of Mg in HNSCC compared with the control in the present study; this however was not statistically significant (P = 0.17).

Zinc plays an important role in immunity, and an interaction between the immune system and cancer development and progression has been established. It is a component of numerous metalloenzymes, and antioxidants and it is important for cell growth and replication, osteogenesis, and immunity. [8],[22] Some studies have found an association of lower Zn intake with the occurrence of certain cancers in some patients, while others have observed no association. [13]

Also while Prasad [23] recorded Zn deficiency in 57% of cases of head and neck cancers, increased level had been previously reported in head and neck cancer. [8],[18] These contradictory findings suggest that additional factors need to be considered in the complex relationship between trace elements and etiopathogenesis of malignant diseases. In this study, decreased level has also been recorded in the HNSCC group relative to control; this difference is also of statistical significance (P = 0.05). Possible explanations for the reduced level of Zn in the study group could include the following: HNSCC directly decreases Zn levels in the body by increased metabolism or take-up of the Zn by the tumoral cells.

Changes in serum zinc levels, serum copper levels, and the Cu/Zn ratio have been reported to be useful indicators of disease activity, prognosis, and response to treatment in hematopoietic malignancies, gastrointestinal malignancies, sarcomas, breast cancers, and epidermoid cancer of the head and neck. [24],[25],[26] The usefulness of this ratio remains to be fully established; whether these changes reflect some undefined, biological processes in the course of malignant transformation or they are merely nonspecific markers of the malignant process remains to be fully elucidated. The mean Cu/Zn ratio in the HNSCC group in this study was low when compared with controls. This difference was also statistically significant (P = 0.04).

Lower plasma levels of selenium have been reported in various malignancies and meta-analyses of observational studies have documented inverse associations between selenium levels and lung cancer [27] and prostate cancer. [28] In this study, there was low serum selenium in the study group compared with the controls; this was a statistically significant difference (P < 0.01). Yadav, et al., [29] have also reported similar findings. This finding may be explained in terms of the level of oxidative stress in cancers patient with a higher values of Se being required in view of its antioxidant property.

Similarly, reduced serum levels of manganese and iron was reported Taysi et al. [20] While in this study a marginal, statistically insignificant (P = 0.36) increase in Mn was noted in HNSCC, the mean serum level of iron was significantly lower in HNSCC compared with controls (P < 0.01). Limited data exist on Mn and cancers, [30] hence no particular trend or defined roles have so far been established for Mn. Significance of this finding cannot at this point be ascertained. However, the lower mean iron could be explained as reflecting the increased demand by both the marrow and the tumor for iron as majority of cancer patients tend to be anemic.


   Conclusion Top


The significantly reduced total antioxidant potential and serum selenium levels are indications of oxidative stress in the head and neck cancer patients with likely negative impact on disease outcome.

 
   References Top

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2.Behrend L, Henderson G, Zwacka RM. Reactive oxygen species in oncogenic transformation. Biochem Soc Trans 2003;31:1441-4.  Back to cited text no. 2
    
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4.Kensler TW, Egner PA, Wang JB, Zhu YR, Zhang BC, Qian GS, et al. Strategies for chemoprevention of liver cancer. Eur J Cancer Prev 2002;11:S58-64.  Back to cited text no. 4
    
5.Halliwell B, Gutteridge JM. Free radicals in biology and medicine. Oxford, United Kingdom: Clarendon Press; 1990.  Back to cited text no. 5
    
6.Cerutti PA, Trump BF. Inflammation and oxidative stress in carcinogenesis. Cancer cells 1991;3:1-7.  Back to cited text no. 6
    
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8.Prasad AS. Zinc: Mechanisms of Host Defense. J Nutr 2007;137:1345-9.  Back to cited text no. 8
    
9.Gowal S, de Giacomi M, Le Boudec JY. A validated mathematical model of cell- mediated immune response to tumor growth. Cancer Res 2007;67:8419-21.  Back to cited text no. 9
    
10.Wintergerst ES, Maggini S, Hornig DH. Contribution of selected vitamins and trace elements to immune function. Ann Nutr Metab 2007;51:301-23.  Back to cited text no. 10
    
11.Arinola OG, Charles-Davies MA. Micronutrient levels in the plasma of Nigerian females with breast cancer. Afr Jour Biotech 2006;7:1620-3.  Back to cited text no. 11
    
12.Navarro SA, Rohan TE. Trace elements and cancer risk: A review of the epidemiologic evidence. Cancer Causes Contr 2007;18:7-27.  Back to cited text no. 12
    
13.Cui Y, Vogt S, Olson N, Glass AG, Rohan TE, Becker JS, et al. Levels of zinc, selenium, calcium, and iron in benign breast tissue and risk of subsequent breast cancer. Cancer Epidemiol Biomarkers Prev 2007;16:1682-5.  Back to cited text no. 13
    
14.Olaniyi JA, Arinola OG. Essential trace elements and antioxidant status in relation to severity of HIV in Nigerian patients. Med Princ Pract 2007;16:420-5.  Back to cited text no. 14
    
15.Margerison ACF, Mann JR. Serum copper, serum caeruloplasmin and erythrocyte sedimentation rate measurements in children with Hodgkin's disease, non-Hodgkin's lymphoma and non malignant lymphadenopathy. Cancer 1985;55:1501-6.  Back to cited text no. 15
    
16.Gupta SK, Singh SP, Shukla VK. Copper, Zinc and Cu/Zn ratio in carcinoma of the gall bladder. J Surg Oncol 2005;91:204-8.  Back to cited text no. 16
    
17.Silverman S, Thompson JS. Serum Zinc and Copper in oral/oropharyngeal carcinoma. Oral Surg 1984;57:34-6.  Back to cited text no. 17
    
18.Fisher GL, Spitler LE, McNeill KL, Rosenblatt LS. Serum copper and zinc levels in melanoma patients. Cancer 1981;47:1838-44.  Back to cited text no. 18
    
19.Aggrawal, SR, Kicker R, Shrivastava S. Serum magnesium in head and neck cancer. Indian J Otolaryngol Head Neck 1981;33:43-6.  Back to cited text no. 19
    
20.Taysi S, Accad F, Oslo C, Dogrib Y. Trace elements and some extracellular antioxidant protein levels in serum of patients with laryngeal cancer. Biol Trace Elem Res 2003;91:11-8.  Back to cited text no. 20
    
21.Groff JL, Gropper SS. Advanced nutrition and human metabolism. Belmont, CA Wadsworth: 2000.  Back to cited text no. 21
    
22.Goyal MM, Kalwar AK, Vyas RK. A study of serum Zinc, selenium, and Copper levels in cancer of the oesophagus patients. Indian J Clin Biochem 2006;21:208-10.  Back to cited text no. 22
    
23.Prasad AS. Zinc deficiency. BMJ 2003;326:409-10.  Back to cited text no. 23
    
24.Zowczak M, Iskia M, Tarlinski L. Analysis of serum copper and zinc concentrations in cancer patients. Biol Trace Elem Res 2001;82:1-8.  Back to cited text no. 24
    
25.Gupta SK, Shukla VK, Vaidya MP, Roy SK, Gupta S. Serum trace elements and Cu/Zn ratio in breast cancer patients. J Surg Oncol 1991;46:178-81.  Back to cited text no. 25
    
26.Garofalo JA, Erlandson E, Strong EW, Lesser M, Grold F, Spiro R, et al. Serum Zinc, Serum Copper and the Cu/Zn Ratio in the Patient with Epidermoid Cancers of the Head and Neck. J Surg Oncol 1980;15:381-6.  Back to cited text no. 26
    
27.Zhuo H, Smith AH, Steinmaus C. Selenium and lung cancer: A quantitative analysis of heterogeneity in the current epidemiological literature. Cancer Epidemiol Biomarkers Prev 2004;13:771-8.  Back to cited text no. 27
    
28.Etminan M, FitzGerald JM, Gleave M, Chambers K. Intake of selenium in the prevention of prostate cancer: A systematic review and meta-analysis. Cancer Causes Control 2005;16:1125-31.  Back to cited text no. 28
    
29.Yadav SP, Gera A, Singh I, Chanda R. Serum Selenium levels in patients with head and neck cancer. J Otolaryngol 2002;31:216-9.  Back to cited text no. 29
    
30.Smith D, Gwiazda R, Bowler R, Roels H, Park R, Taicher C, Lucchini R. Biomarkers of Mn exposure in humans. Am J Ind Med 2007;50:801-11.  Back to cited text no. 30
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1]


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