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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 13  |  Issue : 6  |  Page : 989-992  

Assessment of serum selenium and ceruloplasmin in potentially malignant disorders and oral cancer


1 Department of Oral and Maxillofacial Surgery and Dentistry, ESIC Medical College and PG Institute, Bengaluru, Karnataka, India
2 Department of Dentistry, Sree Narayana Institute of Medical Sciences, Kochi, Kerala, India
3 Department of Oral and Maxillofacial Surgery and Dentistry, King Faisal Hospital, Makkah Al Mukarramah, KSA
4 Department of Oral and Maxillofacial Surgery, School of Dental Science, Krishna Institute of Medical Sciences Deemed to be University, Karad, Maharashtra, India
5 Department of Oral and Maxillofacial Surgery, Royal Dental College, Palakkad, Kerala, India
6 Department of Dentistry, IqCity Medical College and Hospital, Durgapur, West Bengal, India

Date of Submission10-May-2021
Date of Decision17-May-2021
Date of Acceptance18-May-2021
Date of Web Publication10-Nov-2021

Correspondence Address:
Nidhi Ravindran
Department of Dentistry, Sree Narayana Institute of Medical Sciences, Kochi, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpbs.jpbs_380_21

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   Abstract 


Introduction: Despite extensive research and development, potentially malignant disorders (PMDs) of the oral cavity and oral cancer remain a serious concern. Diet and immunity have been identified as important modifiable factors in such diseases. Materials and Methods: A total of 20 patients and 10 healthy individuals, aged 30–60 years, were chosen from the outpatient Department of Oral and Maxillofacial Surgery, Yenepoya Dental College and hospital, Karnataka. The participants were grouped into three: Group 1: (10 healthy individuals), Group 2: (10 oral leukoplakia patients) and Group 3: (10 squamous cell carcinoma patients). Blood was chosen as the investigative medium. Ceruloplasmin was estimated by the diamine oxidase method. The technique of atomic absorption developed by Sir Alan Walsh in 1950 has become the preferred method of elemental analysis of selenium (atomic absorption spectrometer). Statistical analysis of the data obtained was done using one-way ANOVA test and the Turkey multiple comparisons test. Results: The intergroup comparison of ceruloplasmin shows that the mean value of Group I (Control) was 31.746 mg/dl, the mean value of Group II (leukoplakia) was 81.411 mg/dl, and the mean value of Group III (squamous cell carcinoma) was 90.7120 mg/dl. The intergroup comparison of selenium levels shows that the mean value of Group I (Control) was 119.937 (ng/ml), the mean value of Group II (leukoplakia) was 109.17 (ng/ml), and the mean value of Group III (squamous cell carcinoma) was 99.6230 (ng/ml). Conclusion: Antioxidants are an important defense system against free radical damage to cells. Ceruloplasmin and selenium levels in serum could be used as disease markers in leukoplakia and squamous cell carcinoma.

Keywords: Antigen-antibody complex, ceruloplasmin, mouth Neoplasm's, selenium


How to cite this article:
Mampilly MO, Ravindran N, Parambil MS, Nilesh K, Jayagopalan P, Dhamali D. Assessment of serum selenium and ceruloplasmin in potentially malignant disorders and oral cancer. J Pharm Bioall Sci 2021;13, Suppl S2:989-92

How to cite this URL:
Mampilly MO, Ravindran N, Parambil MS, Nilesh K, Jayagopalan P, Dhamali D. Assessment of serum selenium and ceruloplasmin in potentially malignant disorders and oral cancer. J Pharm Bioall Sci [serial online] 2021 [cited 2022 Jun 26];13, Suppl S2:989-92. Available from: https://www.jpbsonline.org/text.asp?2021/13/6/989/330116




   Introduction Top


Malignant as well as premalignant lesions of oral cavity are most common in South India, compared to other parts of the world. Many factors are involved such as chewing and smoking tobacco, alcohol consumption, and occurrence of mechanical irritation.[1] Dietary deficiencies or excesses have been shown to be associated with a number of premalignant lesions. Many studies reported that trace elements such as copper, zinc, iron, ceruloplasmin, and selenium play a major role as either inhibitory or causative agents of these lesions.[2]

Leukoplakia, a premalignant lesion and squamous cell carcinoma, a malignant neoplasm are quite commonly seen occurring in the oral cavity. Betel quid chewing with tobacco remains at the center stage in the etiological risk factors for the high incidence of leukoplakia and oral cancer in India.[3]

Early detection can also be improved by reducing diagnostic delays, reported to be between 3 and 6 months, in the primary care setting. The delay in diagnosis and referral to specialist has a significant negative effect on patient outcome and survival. Thus, there exists a need for a simple, noninvasive, and inexpensive test, widely accessible to physicians in the primary care setting.[4] A very intimate relationship between oxidative challenge and malignancy has been well documented. One significant characteristic of free radical reactivity is lipid peroxidation which results in deleterious effects on cells leading to their damage. Furthermore many chemical carcinogens are shown to be metabolically converted to free radicals which are facilitated by lipid peroxidation.[5]

Epidemiological studies have implicated selenium as a cancer-protective agent. Measurement of serum selenium has recently been the subject of increasing interest because of the toxicological and nutritional importance of the element.[6]

A study was carried out to assess the concentration of serum selenium and serum ceruloplasmin in blood samples from patients with oral leukoplakia and oral squamous cell carcinoma that were observed which helps, not only in the diagnosis of oral cancer, but also in monitoring the tumor burden during and after the treatment, as tumor markers, to aid in the diagnosis and assessment of prognosis of these lesions.


   Materials and Methods Top


The study was approved by the research and ethics committee of the institute. A total of 20 patients and 10 healthy individuals, aged 30–60 years, were chosen from the outpatient Department of Oral and Maxillofacial Surgery, Yenepoya Dental College and hospital, Karnataka. The exclusion criteria were patients with known allergies, autoimmune diseases (except oral lichen planus), diabetes mellitus, hypertension, myocardial infarction, acute infections, acute or chronic liver disease, nephrotic syndrome, or previous history of treatment for cancers (surgery, chemotherapy, and radiotherapy).

The participants were grouped into three: Group I: (10 healthy individuals in control group), Group II: (10 patients who are clinically and histologically diagnosed as oral leukoplakia), and Group III: (10 patients who are histologically and clinically (Stages III and IV) diagnosed as squamous cell carcinoma of the oral cavity). Blood was chosen as the investigative medium. 2 ml of venous blood from each participant was drawn from the medial cubital vein by 24 gauge needles in a sterile disposable syringe set under aseptic measures. The drawn blood was centrifuged and serum separated and was transferred into vacutainer for transport to the laboratory for the estimation of serum selenium and serum ceruloplasmin. Ceruloplasmin was estimated by the diamine oxidase method. The technique of atomic absorption developed by Sir Alan Walsh in 1950 has become the preferred method of elemental analysis of selenium (atomic absorption spectrometer).

Statistical analysis of the data obtained was done using one-way ANOVA test and the Turkey multiple comparisons test. In all the above tests, a P < 0.001 was accepted as indicating high level of statistical significance.


   Results Top


The study was aimed to estimate and compare the levels of selenium and ceruloplasmin in healthy, leukoplakia and squamous cell carcinoma patients.

The normal range is 20–60 mg/dl [Figure 1]. The mean value of Group I (control) was 31.746 mg/dl and standard deviation of 2.65663 with the minimum value of 27.06 and maximum value of 35.87. The mean value of Group II (Leukoplakia) was 81.411 mg/dl and standard deviation of 10.11768 with the minimum value of 59.86 and maximum value of 93.43. The mean value of Group III (squamous cell carcinoma) was 90.7120 mg/dl and standard deviation of 3.64889 with the minimum value of 86.44 and maximum value of 97.09. The mean values when put for statistical analysis by the ANOVA test, the F value was 245.647 with a P = 0.0005 which was statistically significant. The P < 0.0005 when the control group was compared to leukoplakia and squamous cell carcinoma. The P = 0.008 when the leukoplakia group was compared with the squamous cell carcinoma group [Table 1].
Figure 1: Depicts the ceruloplasmin levels (mg/dl) in participants in different groups

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Table 1: Intergroup comparison of ceruloplasmin (mg/dl) levels

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The normal range is 115–35 ng/ml [Figure 2]. The mean value of Group I (control) was 119.937 (ng/ml) and standard deviation of 2.10956 with the minimum value of 116.09 and maximum value of 122.54.The mean value of Group II (Leukoplakia) was 109.17 (ng/ml) and standard deviation of 3.82363 with the minimum value of 102.66 and maximum value of 115.04. The mean value of Group III (Squamous cell carcinoma) was 99.6230 (ng/ml) and standard deviation of 4.05302 with the minimum value of 92.08 and maximum value of 104.61. The mean values when put for statistical analysis by the ANOVA test, the F = 87.293 with a P < 0.0005 which was statistically significant. The P = 0.0005 when the following groups was compared: control versus leukoplakia, control versus squamous cell carcinoma, and leukoplakia versus squamous cell carcinoma [Table 2].
Figure 2: Depicts the selenium levels (ng/ml) in participants in different groups

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Table 2: Intergroup comparison of selenium (ng/ml) levels

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   Discussion Top


The death rate associated with oral cancer is actually very high, not because it is difficult to detect or diagnose, but because cancer is often discovered at an advanced stage. It also goes unnoticed by the patient in its early stages because it thrives without causing many symptoms. Due to the lack of a robust screening program, late-stage identification is still a normal occurrence.[7] Cancer being a genetic disorder involves multiple alterations of the genome progressively accumulated during a protracted period, the overall effects of which surpass the inherent reparative ability of the cell. In the course of its progression, visible physical changes are taking place at the cellular level and at the resultant tissue level. These alterations include genetic changes, epigenetic changes, surface alterations, and alterations in intercellular interactions. The sum of these physical and morphological alterations is of diagnostic and prognostic relevance.[8],[9],[10]

Trace elements have been extensively studied in recent years to assess whether they have any modifying effects in the etiology of cancer. Copper, iron, and selenium are essential for numerous enzymes, and therefore, it is reasonable to assume that variations in serum level of these biochemical markers may be associated with the pathogenesis of oral cancer.[11]

The normal range of serum selenium is 115–135 ng/ml. This study showed lower levels of selenium in leukoplakia (mean = 109.1700) and squamous cell carcinoma (mean = 99.6230) patients when compared to healthy individuals (mean = 119.9370). This is in accordance with the results of Krishnaswamy et al.[12] and Khanna and Karjodkar[11] who showed that selenium levels showed marked decrease in the cancer group and are the best predictors for the occurrence of lesions and show that these immunological and biological markers may be associated with the pathogenesis of oral premalignant and malignant lesions and their progressions.

The decrease in the serum selenium level in oral squamous cell carcinoma and leukoplakia patients can be attributed to the protective role as antioxidant in cancer.

The normal range of serum ceruloplasmin is 20–60 mg/dl. In this study, the findings indicated higher levels of ceruloplasmin in patients with leukoplakia (mean = 81.4110) and squamous cell carcinoma (mean = 90.7120) when compared to healthy (mean = 31.7460) individuals. These results are in agreement with the findings of Jayadeep et al.[13] and Alper et al.[14] who showed that ceruloplasmin levels were significantly increased in oral leukoplakia and cancer.

Serum ceruloplasmin has been shown to be a potent antioxidant and scavenger of free radicals and superoxide ions, and the findings of this study strongly support this hypothesis. The explanation appears to be an increase in serum cuproenzyme, ceruloplasmin as a result of decreased catabolism of this enzyme, combined with increased compensatory antioxidant defenses in serum to combat the transformation of nonmalignant cells to malignant cells.[15]


   Conclusion Top


Antioxidants constitute a very important defense system against the free radical injury of cells. Not only during minor free radical injurious process, they come into play but also when malignancy develops. To combat the generation of preoxidant states, the human body generates excessive amounts of antioxidant elements such as ceruloplasmin, glutathione, and α-tocopherol whereas the levels of zinc and selenium decrease. Monitoring the levels of ceruloplasmin and selenium in serum could be utilized as disease markers in leukoplakia and squamous cell carcinoma.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Kumar M, Nanavati R, Modi TG, Dobariya C. Oral cancer: Etiology and risk factors: A review. J Cancer Res Ther 2016;12:458-63.  Back to cited text no. 1
    
2.
Bhattacharya PT, Misra SR, Hussain M. Nutritional aspects of essential trace elements in oral health and disease: An extensive review. Scientifica (Cairo) 2016;2016:5464373.  Back to cited text no. 2
    
3.
Yardimci G, Kutlubay Z, Engin B, Tuzun Y. Precancerous lesions of oral mucosa. World J Clin Cases 2014;2:866-72.  Back to cited text no. 3
    
4.
Nekhlyudov L, Latosinsky S. The interface of primary and oncology specialty care: From symptoms to diagnosis. J Natl Cancer Inst Monogr 2010;2010:11-7.  Back to cited text no. 4
    
5.
Rahal A, Kumar A, Singh V, Yadav B, Tiwari R, Chakraborty S, et al. Oxidative stress, prooxidants, and antioxidants: The interplay. Biomed Res Int 2014;2014:761264.  Back to cited text no. 5
    
6.
Kadkol S, Diamond AM. The Interaction between Dietary Selenium Intake and Genetics in Determining Cancer Risk and Outcome. Nutrients 2020;12:2424. doi: 10.3390/nu12082424.  Back to cited text no. 6
    
7.
Garg P, Karjodkar F. “Catch Them before it Becomes Too Late”-Oral Cancer Detection. Report of two cases and review of diagnostic AIDS in cancer detection. Int J Prev Med 2012;3:737-41.  Back to cited text no. 7
    
8.
Warren S, Gates O. Multiple primary malignant tumors: A survey of the literature and statistical study. Am J Cancer 1932;16:1358-414.  Back to cited text no. 8
    
9.
Tsao AS, Kim ES, Hong WK. Chemoprevention of cancer. CA Cancer J Clin 2004;54:150-80.  Back to cited text no. 9
    
10.
Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 1953;6:963-8.  Back to cited text no. 10
    
11.
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.  Back to cited text no. 11
    
12.
Krishnaswamy K, Prasad MP, Krishna TP, Pasricha S. A case control study of selenium in cancer. Indian J Med Res 1993;98:124-8.  Back to cited text no. 12
    
13.
Jayadeep A, Raveendran Pillai K, Kannan S, Nalinakumari KR, Mathew B, Krishnan Nair M, et al. Serum levels of copper, zinc, iron and ceruplasmin in oral leukoplakia and squamous cell carcinoma. J Exp Clin Cancer Res 1997;16:295-300.  Back to cited text no. 13
    
14.
Alper H, Fischer C, Nevoigt E, Stephanopoulos G. Tuning genetic control through promoter engineering. Proc Natl Acad Sci U S A 2005;102:12678-83.  Back to cited text no. 14
    
15.
Mohammed AA, Youssef JM, Metwally SS, Anees MM. Evaluation of the serum ceruloplasmin level before and after non-surgical periodontal therapy in patients with chronic periodontitis. Stomatological Dis Sci 2018;2:3.  Back to cited text no. 15
    


    Figures

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