Original Article
Status of trace elements in saliva of oral precancer and oral cancer patients ABSTRACT Background: Several studies in recent years have linked association between micronutrient levels and various forms of cancer. Copper and zinc have been the most researched micronutrients. Aim: The aim of the study was to evaluate the levels of copper, zinc and iron in saliva of patients with oral leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma. Results: There was a highly significant increase in the level of salivary copper in oral submucous fibrosis patients when compared to controls (P = 0.001). Salivary copper levels were also elevated in oral leukoplakia and oral cancer patients (P = 0.01). There was a significant decrease in the salivary zinc levels in all three study groups when compared to controls (P = 0.001). A highly significant reduction in salivary iron levels was noticed oral submucous fibrosis group. The copper to zinc ratio significantly increased in all the study groups when compared to controls. Conclusion: Results suggest that salivary copper zinc and iron could be used as biomarkers for oral precancer and cancer. KEY WORDS: Copper, iron, leukoplakia, oral squamous cell carcinoma, saliva, zinc
INTRODUCTION India has one of the highest incidences of oral cancer in the world.[1] The development of cancer is a multistep process arising from pre‑existing potentially malignant lesions. Oral leukoplakia (OL) is the most common precancer representing 85% of such lesions.[2] Alcohol, viruses, genetic mechanisms, candida and chronic irritation have modifying effects in the etiology of oral cancer.[2] Trace elements are regarded as versatile anti‑cancer agents that regulate various biological mechanisms.[3] Many researchers have observed association between trace elements and cancer mortality.[4] Decrease in contents of Copper (Cu) and Zinc (Zn) in the blood of patients with head and neck cancer.[5,6] Most of the molecules that are found in the body fluids like blood and urine are also found in the saliva, although in lesser concentration thus making saliva an important diagnostic tool.[7] The present study was conducted to evaluate the levels of Cu Zn and Iron (Fe) in oral potentially malignant disorders and oral squamous cell carcinoma. MATERIALS AND METHODS Two hundred patients reporting to the department of Oral medicine and Radiology were enrolled into a cross sectional case control study over a period 3 years from August 2009 to August 2012. 146
Ethical clearance for the study was obtained from the institutional ethical committee. They were divided into four equal study groups with 50 subjects each. The first study group OL consisted of 50 patients of histopathologically confirmed cases of oral leukoplakia (45 cases of homogenous leukoplakia and 5 cases of speckled leukoplakia). The second study group consisted of 50 histopathologically confirmed patients with oral submucous fibrosis (OSMF). The third study group consisted of 50 histopathologically confirmed cases of oral squamous cell carcinoma (OSSC). The fourth study group consisted of 50 age and gender matched healthy controls (HC). Detailed history and clinical examination was done for each of the study subjects. After informed consent 5 ml of unstimulated saliva was collected from each of the patient using the spit method. Standard pre‑investigative protocol (no consumption of food/ no smoking for an hour before saliva collection) for saliva collection was followed which was carried out between 9 and 11 A.M.[8] The saliva was centrifuged at 2500 rpm for 10 min at 0‑5°C. The supernatants were stored frozen at −20°C until time of analysis. For the analysis of salivary Cu and Zn levels a series of standard Cu solutions were made raging from 1 to 10 ppm. The unknown samples (study samples) were analysed in comparison to the standardized Cu solutions using the GBC Avanta atom absorption spectrophotometer [Figure 1]. Similar procedure was followed for estimation of salivary Zn. Salivary
Shishir Ram Shetty, Subhas Babu, Suchetha Kumari1, Pushparaja Shetty2, Shruthi Hegde, Arvind Karikal3 Departments of Oral Medicine and Radiology, 2Oral Pathology, 3Oral Surgery, AB Shetty memorial Institute of Dental Science, 1 Department of Biochemistry, KS Hegde Medical Academy, Nitte University, Mangalore, Karnataka, India For correspondence: Dr. Shishir Ram Shetty, Department of Oral Medicine and Radiology, AB Shetty Memorial Institute of Dental, Sciences, Nitte University, Mangalore, India E‑mail: drshishirshettyomr@ yahoo.com
Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.137973 PMID: *** Quick Response Code:
Journal of Cancer Research and Therapeutics - January-March 2015 - Volume 11 - Issue 1
Shetty, et al.: Salivary trace elements
Fe was measured by the Bathophenanthroline method. 100 µL of the saliva sample was taken in a clean microfuge tube and made upto 250µL with the addition of deionised water. 500 µL of protein precipitating solution was added to the diluted sample. The mixture was then centrifuged at 2000 rpm for 10 min. 500 µL of the supernatant was then added to 500 µL of chromogen solution (25 mg Bathophenanthroline sulfonate dissolved in 100 mL of sodium acetate (2M). The optical density of the pink colour formed was read immediately (within 10 min) at 535 nm against a blank treated in a similar method as the test wherein the sample was replaced with deionised water. The concentration of iron in the sample was deduced by plotting the optical densities of the test against the standard graph. The concentration that obtained was multiplied by the dilution factor (2.5). The data were statically analyzed by the ANOVA and HSD Turkey’s test using the SPSS version 17 software. RESULTS The mean salivary Cu levels in group HC, OSMF, OL and OSCC were 46.07 ± 4.56 µg/dL, 87.45 ± 2.67 µg/dL, 55.54 ± 2.57 µg/dL and 57.87 ± 4.98 µg/dL, respectively [Figure 2]. There was a highly significant (P = 0.001) increase in the levels of Cu in the OSMF group when compared to controls. The Cu levels were significantly elevated (P = 0.01) in the OL and OSCC groups when compared to HC. However there was no statistically significant difference (P > 0.05) when the groups OL and OSCC were intercompared. The mean salivary Zn levels in group HC, OSMF, OL and OSCC were
35.78 ± 3.97 µg/dL, 24.67 ± 4.86 µg/dL, 27.33 ± 3.05 µg/ dL and 15.23 ± 2.93 µg/dL, respectively. There was a highly significant reduction (P = 0.001) in the salivary Zn levels in all three study groups OSMF, OL and OSCC when compared to HC [Figure 3]. There was no significant difference (P > 0.05) in the mean zinc levels between the OL and OSMF groups. The Cu/Zn ratio was higher in all three study groups OSMF, OL and OSCC when compared to the HC [Figure 4]. The mean salivary Fe levels in group HC, OSMF, OL and OSCC were 76.07 ± 3.65 µg/dL, 35.67 ± 1.34 µg/dL, 47.08 ± 3.33 µg/dL and 36.78 ± 2.23 µg/dL, respectively [Figure 5]. The salivary Fe levels were least in the OSMF group. DISCUSSION Trace elements like Cu and Zn have a role in the anti‑carcinogen defense system of the human body. Cu is involved in the cell metabolism, as a part of various enzymes tyrosinase, uricase and cytochrome oxidase, which are mainly concerned with oxidation reactions.[8] It was observed that mean serum Cu levels were significantly higher in the sera of patients with oral premalignant and malignant lesions.[9] In our study there was an elevation of the salivary Cu in the OL and OSCC group. Although few serum studies have been carried out in the recent past only one salivary study regarding status of Cu in saliva has been published recently wherein they reported an increase in the salivary Cu levels in the saliva of subjects with OSCC and OL when compared to controls.[10] In our study we used a larger sample size in each of the study groups and also intercompared the salivary Cu levels between group OSMF, OL and OSCC wherein we found a significant increase in the levels of salivary Cu levels in group OSMF. The reason for the increase in Cu levels in serum is due to its ability to induce an intrinsic protein based enzyme (lysl‑oxidase) in the connective tissue that crosslinks collagen and elastin which is an important factor in etiopathogenesis of OSMF.[11]
Figure 2: Graph showing salivary Copper levels in study groups Figure 1: Laboratory procedures (atom absorption spectrophotometry)
Figure 3: Graph showing mean salivary Zinc levels in study groups
Figure 4: Graph showing Copper to zinc ratio in study groups
Journal of Cancer Research and Therapeutics - January-March 2015 - Volume 11 - Issue 1
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Shetty, et al.: Salivary trace elements
biological markers in oral carcinogenesis. The significant and encouraging findings of the present study thus validate and reinforce that; salivary micronutrient analysis can be used as an efficient, non‑invasive, patient‑friendly tool for the early diagnosis of PMD and OSCC for planning comprehensive treatment protocol. REFERENCES Figure 5: Graph showing mean salivary iron levels in study groups
The role of Cu in carcinogenesis is highlighted by its involvement in Fenton reaction → H2O2 + Cu (I)→Cu (II) OH + OH−. Cu also activates angiogenic factors like vascular endothelial growth factor (VEGF), Tumour Necrosis Factor (TNF) alpha and Interleukin‑1(IL‑1).[12] The levels of cerruloplasmin which is a Cu transporting protein, increases 4‑8 times when tumours become palpable.[13] Zn acts as a cofactor for Cu‑Zn superoxide dismutase enzyme that is a part of the primary antioxidant system of all vertebrates.[16] Some studies have revealed lower Zn level in serum of patients with potentially premalignant disorders like in OL.[15,16] This might be because of the consumption of Zn in counter reacting to oxidants which are generated due to tobacco or high Cu of areca quid metabolism.[17] In our study the salivary levels of Zn was significantly reduced in all three study groups when compared to controls. Although there was no statistically significant difference between the salivary Zn levels in OL and OSMF groups. Researchers also believe that Zn inhibits the invasive/migration activities in malignant prostate cells.[18] Further Zn is said to have an antioxidant role in prevention of carcinogenesis by two mechanisms. Firstly, the protection of sulfhydryl groups against oxidation and the inhibition of the production of reactive oxygen species by transition metals. Secondly, supra‑physiological concentration of Zn has antioxidant‑like effects in organelle‑based systems and isolated cell‑based systems. Thus, a decrease in the Zn levels and Zn dependent SOD is said to be an indicator of early mucosal changes preceding carcinogenesis.[19] In our study we observed decreased salivary Fe which was observed in OSMF, OL and OSCC patients. Decreased Fe levels in OSMF patients might be due to utilization of Fe in collagen synthesis.[20] It has been stated that the decrease in Fe content leads to decrease in epithelial vascularity which results in increased penetration of arecoline which leads to fibrosis.[21] Inadequate nutrition due to burning sensation and erosions in OSMF patients and increased tumour burden in OSCC patients are considered to be important factors for iron depletion.[22] CONCLUSION In the recent years a surge in number of studies involving serum levels of trace elements like Cu, Zn and Fe in various malignancies have been observed. The results of the study reveal that salivary levels Cu, Zn and Fe could be used as 148
1. Hamada GS, Bos AJ, Kasuga H, Hirayama T. Comparative epidemiology of oral cancer in Brazil and India. Tokai J Exp. Clin Med 1991;16:63‑72. 2. Bouquot JE, Whitaker SB. Oral Leukoplakia rationale for diagnosis and prognosis of its clinical subtypes or phases. Quintessence Int 1994;25:133‑40. 3. Koyama H. Trace elements: Mechanistic action of anticarcinogenic action action. Nippon Rinsho 1994;54:52‑8. 4. Ames BN. Micronutrients prevent cancer and delay aging. Toxicol Lett 1999; 28:102‑3. 5. Vyas RK, Gupta AP, Gupta A, Aeron AK. Serum Copper, zinc, Magnesium and cadmium levels in various human disease. Indian J Med Res 1982;76:301‑4. 6. Slavkin HC. Protecting the mouth against microbial infections. J Am Dent Assoc 1998;129:1025‑30. 7. Al rawi NH, Talabani NG. Quatitative análisis of trace elements in saliva of oral cancer patients. J Coll Dent 2005;17:32‑5. 8. Margalith EJ, Schenker JG, Chevion M. Copper and zinc levels in normal and malignant tissues. Cancer 1983;52:868‑72. 9. Khanna SS, Karjodkar FR. Circulating immune complexes and trace elements (Copper, Iron and Selenium) as markers in oral precancer and cancer: A randomised, controlled clinical trial. Head Face Med 2006;2:33. 10. Ayinapmudi KB, Narasimhan M. Salivary Copper and zinc levels in oralpremalignant and malignant lesions. J Oral Maxillofac Pathol 2012;16:178‑82. 11. Tadakamadla J, Kumar S, GP M. Evaluation of serum copper and iron levels among oral submucous fibrosis patients. Med Oral Patol Oral Cir Bucal 2011;16:e870‑3. 12. Hannen EJ, Riediger D. The quantification of angiogenesis in relation to metastasis in oral cancer: A review. Int J Oral Maxillofac Surg 2004;33:2‑7. 13. Nasulewicz A, Mazur A, Opolski A. Role of copper in tumour angiogenesis: Clinical implications. J Trace Elem Med Biol 2004;18:1‑8. 14. Miceli MV, Tatejr DJ, Alcock NW, Newsome DA. Zinc deficiency and oxidative stress in the retina of pigmented rats. Invest Ophthalmol Vis Sci 1999;40:1238‑44. 15. Jayadeep A, Raveendran PK, Kannan S, Nalinakumari KR, Mathew B, Krishnan NM. Serum levels of copper, zinc, iron and ceruloplasmin in oral leukoplakia and Squamous cell carcinoma. J Exp Clin Can Res 1997;16:295‑300. 16. Swain N, Ray JG. Altered trace element level and antioxidant activity in whole blood of oral leukoplakia and cancer patients in comparison with healthy controls. Int J Oral Maxillofac Pathol 2011;2:2‑6. 17. Bose SC, Singh M, Vyas P, Singh M. Plasma zinc antioxidant vitamins, glutathione levels and total antioxidant activity in oral leukoplakia. Dent Res J (Isfahan) 2012;9:158‑61. 18. Costello LC, Feng P, Milon B, Tan M, Franklin RB. Role of zinc in the pathogenesis and treatment of prostate cancer: Critical issues to resolve. Prostate Cancer Prostatic Dis 2004;7:111‑7. 19. Powell SR . The antioxidant properties of Zinc. J Nutr 2000;130:1447S‑54S. 20. Anuradha CD, Devi CS. Serum protein, ascorbic acid and iron and tissue collagen in oral submucous fibrosis‑‑a preliminary study. Indian J Med Res 1993;98:147‑51. 21. Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S.
Journal of Cancer Research and Therapeutics - January-March 2015 - Volume 11 - Issue 1
Shetty, et al.: Salivary trace elements
Oral submucous fibrosis: Review on aetiology and pathogenesis. Oral Oncol 2006;42:561 22. Khanna S. Immunological and Biochemical Markers in Oral Carcinogenesis: The Public Health Perspective. Int J Environ Res Public Health 2008;5:418‑22.
Cite this article as: Shetty SR, Babu S, Kumari S, Shetty P, Hegde S, Karikal A. Status of trace elements in saliva of oral precancer and oral cancer patients. J Can Res Ther 2015;11:146-9. Source of Support: Nil, Conflict of Interest: None declared.
Journal of Cancer Research and Therapeutics - January-March 2015 - Volume 11 - Issue 1
149
Copyright of Journal of Cancer Research & Therapeutics is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Status of trace elements in saliva of oral precancer and oral cancer patients ABSTRACT Background: Several studies in recent years have linked association between micronutrient levels and various forms of cancer. Copper and zinc have been the most researched micronutrients. Aim: The aim of the study was to evaluate the levels of copper, zinc and iron in saliva of patients with oral leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma. Results: There was a highly significant increase in the level of salivary copper in oral submucous fibrosis patients when compared to controls (P = 0.001). Salivary copper levels were also elevated in oral leukoplakia and oral cancer patients (P = 0.01). There was a significant decrease in the salivary zinc levels in all three study groups when compared to controls (P = 0.001). A highly significant reduction in salivary iron levels was noticed oral submucous fibrosis group. The copper to zinc ratio significantly increased in all the study groups when compared to controls. Conclusion: Results suggest that salivary copper zinc and iron could be used as biomarkers for oral precancer and cancer. KEY WORDS: Copper, iron, leukoplakia, oral squamous cell carcinoma, saliva, zinc
INTRODUCTION India has one of the highest incidences of oral cancer in the world.[1] The development of cancer is a multistep process arising from pre‑existing potentially malignant lesions. Oral leukoplakia (OL) is the most common precancer representing 85% of such lesions.[2] Alcohol, viruses, genetic mechanisms, candida and chronic irritation have modifying effects in the etiology of oral cancer.[2] Trace elements are regarded as versatile anti‑cancer agents that regulate various biological mechanisms.[3] Many researchers have observed association between trace elements and cancer mortality.[4] Decrease in contents of Copper (Cu) and Zinc (Zn) in the blood of patients with head and neck cancer.[5,6] Most of the molecules that are found in the body fluids like blood and urine are also found in the saliva, although in lesser concentration thus making saliva an important diagnostic tool.[7] The present study was conducted to evaluate the levels of Cu Zn and Iron (Fe) in oral potentially malignant disorders and oral squamous cell carcinoma. MATERIALS AND METHODS Two hundred patients reporting to the department of Oral medicine and Radiology were enrolled into a cross sectional case control study over a period 3 years from August 2009 to August 2012. 146
Ethical clearance for the study was obtained from the institutional ethical committee. They were divided into four equal study groups with 50 subjects each. The first study group OL consisted of 50 patients of histopathologically confirmed cases of oral leukoplakia (45 cases of homogenous leukoplakia and 5 cases of speckled leukoplakia). The second study group consisted of 50 histopathologically confirmed patients with oral submucous fibrosis (OSMF). The third study group consisted of 50 histopathologically confirmed cases of oral squamous cell carcinoma (OSSC). The fourth study group consisted of 50 age and gender matched healthy controls (HC). Detailed history and clinical examination was done for each of the study subjects. After informed consent 5 ml of unstimulated saliva was collected from each of the patient using the spit method. Standard pre‑investigative protocol (no consumption of food/ no smoking for an hour before saliva collection) for saliva collection was followed which was carried out between 9 and 11 A.M.[8] The saliva was centrifuged at 2500 rpm for 10 min at 0‑5°C. The supernatants were stored frozen at −20°C until time of analysis. For the analysis of salivary Cu and Zn levels a series of standard Cu solutions were made raging from 1 to 10 ppm. The unknown samples (study samples) were analysed in comparison to the standardized Cu solutions using the GBC Avanta atom absorption spectrophotometer [Figure 1]. Similar procedure was followed for estimation of salivary Zn. Salivary
Shishir Ram Shetty, Subhas Babu, Suchetha Kumari1, Pushparaja Shetty2, Shruthi Hegde, Arvind Karikal3 Departments of Oral Medicine and Radiology, 2Oral Pathology, 3Oral Surgery, AB Shetty memorial Institute of Dental Science, 1 Department of Biochemistry, KS Hegde Medical Academy, Nitte University, Mangalore, Karnataka, India For correspondence: Dr. Shishir Ram Shetty, Department of Oral Medicine and Radiology, AB Shetty Memorial Institute of Dental, Sciences, Nitte University, Mangalore, India E‑mail: drshishirshettyomr@ yahoo.com
Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.137973 PMID: *** Quick Response Code:
Journal of Cancer Research and Therapeutics - January-March 2015 - Volume 11 - Issue 1
Shetty, et al.: Salivary trace elements
Fe was measured by the Bathophenanthroline method. 100 µL of the saliva sample was taken in a clean microfuge tube and made upto 250µL with the addition of deionised water. 500 µL of protein precipitating solution was added to the diluted sample. The mixture was then centrifuged at 2000 rpm for 10 min. 500 µL of the supernatant was then added to 500 µL of chromogen solution (25 mg Bathophenanthroline sulfonate dissolved in 100 mL of sodium acetate (2M). The optical density of the pink colour formed was read immediately (within 10 min) at 535 nm against a blank treated in a similar method as the test wherein the sample was replaced with deionised water. The concentration of iron in the sample was deduced by plotting the optical densities of the test against the standard graph. The concentration that obtained was multiplied by the dilution factor (2.5). The data were statically analyzed by the ANOVA and HSD Turkey’s test using the SPSS version 17 software. RESULTS The mean salivary Cu levels in group HC, OSMF, OL and OSCC were 46.07 ± 4.56 µg/dL, 87.45 ± 2.67 µg/dL, 55.54 ± 2.57 µg/dL and 57.87 ± 4.98 µg/dL, respectively [Figure 2]. There was a highly significant (P = 0.001) increase in the levels of Cu in the OSMF group when compared to controls. The Cu levels were significantly elevated (P = 0.01) in the OL and OSCC groups when compared to HC. However there was no statistically significant difference (P > 0.05) when the groups OL and OSCC were intercompared. The mean salivary Zn levels in group HC, OSMF, OL and OSCC were
35.78 ± 3.97 µg/dL, 24.67 ± 4.86 µg/dL, 27.33 ± 3.05 µg/ dL and 15.23 ± 2.93 µg/dL, respectively. There was a highly significant reduction (P = 0.001) in the salivary Zn levels in all three study groups OSMF, OL and OSCC when compared to HC [Figure 3]. There was no significant difference (P > 0.05) in the mean zinc levels between the OL and OSMF groups. The Cu/Zn ratio was higher in all three study groups OSMF, OL and OSCC when compared to the HC [Figure 4]. The mean salivary Fe levels in group HC, OSMF, OL and OSCC were 76.07 ± 3.65 µg/dL, 35.67 ± 1.34 µg/dL, 47.08 ± 3.33 µg/dL and 36.78 ± 2.23 µg/dL, respectively [Figure 5]. The salivary Fe levels were least in the OSMF group. DISCUSSION Trace elements like Cu and Zn have a role in the anti‑carcinogen defense system of the human body. Cu is involved in the cell metabolism, as a part of various enzymes tyrosinase, uricase and cytochrome oxidase, which are mainly concerned with oxidation reactions.[8] It was observed that mean serum Cu levels were significantly higher in the sera of patients with oral premalignant and malignant lesions.[9] In our study there was an elevation of the salivary Cu in the OL and OSCC group. Although few serum studies have been carried out in the recent past only one salivary study regarding status of Cu in saliva has been published recently wherein they reported an increase in the salivary Cu levels in the saliva of subjects with OSCC and OL when compared to controls.[10] In our study we used a larger sample size in each of the study groups and also intercompared the salivary Cu levels between group OSMF, OL and OSCC wherein we found a significant increase in the levels of salivary Cu levels in group OSMF. The reason for the increase in Cu levels in serum is due to its ability to induce an intrinsic protein based enzyme (lysl‑oxidase) in the connective tissue that crosslinks collagen and elastin which is an important factor in etiopathogenesis of OSMF.[11]
Figure 2: Graph showing salivary Copper levels in study groups Figure 1: Laboratory procedures (atom absorption spectrophotometry)
Figure 3: Graph showing mean salivary Zinc levels in study groups
Figure 4: Graph showing Copper to zinc ratio in study groups
Journal of Cancer Research and Therapeutics - January-March 2015 - Volume 11 - Issue 1
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Shetty, et al.: Salivary trace elements
biological markers in oral carcinogenesis. The significant and encouraging findings of the present study thus validate and reinforce that; salivary micronutrient analysis can be used as an efficient, non‑invasive, patient‑friendly tool for the early diagnosis of PMD and OSCC for planning comprehensive treatment protocol. REFERENCES Figure 5: Graph showing mean salivary iron levels in study groups
The role of Cu in carcinogenesis is highlighted by its involvement in Fenton reaction → H2O2 + Cu (I)→Cu (II) OH + OH−. Cu also activates angiogenic factors like vascular endothelial growth factor (VEGF), Tumour Necrosis Factor (TNF) alpha and Interleukin‑1(IL‑1).[12] The levels of cerruloplasmin which is a Cu transporting protein, increases 4‑8 times when tumours become palpable.[13] Zn acts as a cofactor for Cu‑Zn superoxide dismutase enzyme that is a part of the primary antioxidant system of all vertebrates.[16] Some studies have revealed lower Zn level in serum of patients with potentially premalignant disorders like in OL.[15,16] This might be because of the consumption of Zn in counter reacting to oxidants which are generated due to tobacco or high Cu of areca quid metabolism.[17] In our study the salivary levels of Zn was significantly reduced in all three study groups when compared to controls. Although there was no statistically significant difference between the salivary Zn levels in OL and OSMF groups. Researchers also believe that Zn inhibits the invasive/migration activities in malignant prostate cells.[18] Further Zn is said to have an antioxidant role in prevention of carcinogenesis by two mechanisms. Firstly, the protection of sulfhydryl groups against oxidation and the inhibition of the production of reactive oxygen species by transition metals. Secondly, supra‑physiological concentration of Zn has antioxidant‑like effects in organelle‑based systems and isolated cell‑based systems. Thus, a decrease in the Zn levels and Zn dependent SOD is said to be an indicator of early mucosal changes preceding carcinogenesis.[19] In our study we observed decreased salivary Fe which was observed in OSMF, OL and OSCC patients. Decreased Fe levels in OSMF patients might be due to utilization of Fe in collagen synthesis.[20] It has been stated that the decrease in Fe content leads to decrease in epithelial vascularity which results in increased penetration of arecoline which leads to fibrosis.[21] Inadequate nutrition due to burning sensation and erosions in OSMF patients and increased tumour burden in OSCC patients are considered to be important factors for iron depletion.[22] CONCLUSION In the recent years a surge in number of studies involving serum levels of trace elements like Cu, Zn and Fe in various malignancies have been observed. The results of the study reveal that salivary levels Cu, Zn and Fe could be used as 148
1. Hamada GS, Bos AJ, Kasuga H, Hirayama T. Comparative epidemiology of oral cancer in Brazil and India. Tokai J Exp. Clin Med 1991;16:63‑72. 2. Bouquot JE, Whitaker SB. Oral Leukoplakia rationale for diagnosis and prognosis of its clinical subtypes or phases. Quintessence Int 1994;25:133‑40. 3. Koyama H. Trace elements: Mechanistic action of anticarcinogenic action action. Nippon Rinsho 1994;54:52‑8. 4. Ames BN. Micronutrients prevent cancer and delay aging. Toxicol Lett 1999; 28:102‑3. 5. Vyas RK, Gupta AP, Gupta A, Aeron AK. Serum Copper, zinc, Magnesium and cadmium levels in various human disease. Indian J Med Res 1982;76:301‑4. 6. Slavkin HC. Protecting the mouth against microbial infections. J Am Dent Assoc 1998;129:1025‑30. 7. Al rawi NH, Talabani NG. Quatitative análisis of trace elements in saliva of oral cancer patients. J Coll Dent 2005;17:32‑5. 8. Margalith EJ, Schenker JG, Chevion M. Copper and zinc levels in normal and malignant tissues. Cancer 1983;52:868‑72. 9. Khanna SS, Karjodkar FR. Circulating immune complexes and trace elements (Copper, Iron and Selenium) as markers in oral precancer and cancer: A randomised, controlled clinical trial. Head Face Med 2006;2:33. 10. Ayinapmudi KB, Narasimhan M. Salivary Copper and zinc levels in oralpremalignant and malignant lesions. J Oral Maxillofac Pathol 2012;16:178‑82. 11. Tadakamadla J, Kumar S, GP M. Evaluation of serum copper and iron levels among oral submucous fibrosis patients. Med Oral Patol Oral Cir Bucal 2011;16:e870‑3. 12. Hannen EJ, Riediger D. The quantification of angiogenesis in relation to metastasis in oral cancer: A review. Int J Oral Maxillofac Surg 2004;33:2‑7. 13. Nasulewicz A, Mazur A, Opolski A. Role of copper in tumour angiogenesis: Clinical implications. J Trace Elem Med Biol 2004;18:1‑8. 14. Miceli MV, Tatejr DJ, Alcock NW, Newsome DA. Zinc deficiency and oxidative stress in the retina of pigmented rats. Invest Ophthalmol Vis Sci 1999;40:1238‑44. 15. Jayadeep A, Raveendran PK, Kannan S, Nalinakumari KR, Mathew B, Krishnan NM. Serum levels of copper, zinc, iron and ceruloplasmin in oral leukoplakia and Squamous cell carcinoma. J Exp Clin Can Res 1997;16:295‑300. 16. Swain N, Ray JG. Altered trace element level and antioxidant activity in whole blood of oral leukoplakia and cancer patients in comparison with healthy controls. Int J Oral Maxillofac Pathol 2011;2:2‑6. 17. Bose SC, Singh M, Vyas P, Singh M. Plasma zinc antioxidant vitamins, glutathione levels and total antioxidant activity in oral leukoplakia. Dent Res J (Isfahan) 2012;9:158‑61. 18. Costello LC, Feng P, Milon B, Tan M, Franklin RB. Role of zinc in the pathogenesis and treatment of prostate cancer: Critical issues to resolve. Prostate Cancer Prostatic Dis 2004;7:111‑7. 19. Powell SR . The antioxidant properties of Zinc. J Nutr 2000;130:1447S‑54S. 20. Anuradha CD, Devi CS. Serum protein, ascorbic acid and iron and tissue collagen in oral submucous fibrosis‑‑a preliminary study. Indian J Med Res 1993;98:147‑51. 21. Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S.
Journal of Cancer Research and Therapeutics - January-March 2015 - Volume 11 - Issue 1
Shetty, et al.: Salivary trace elements
Oral submucous fibrosis: Review on aetiology and pathogenesis. Oral Oncol 2006;42:561 22. Khanna S. Immunological and Biochemical Markers in Oral Carcinogenesis: The Public Health Perspective. Int J Environ Res Public Health 2008;5:418‑22.
Cite this article as: Shetty SR, Babu S, Kumari S, Shetty P, Hegde S, Karikal A. Status of trace elements in saliva of oral precancer and oral cancer patients. J Can Res Ther 2015;11:146-9. Source of Support: Nil, Conflict of Interest: None declared.
Journal of Cancer Research and Therapeutics - January-March 2015 - Volume 11 - Issue 1
149
Copyright of Journal of Cancer Research & Therapeutics is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
