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ORIGINAL RESEARCH  
Year : 2016  |  Volume : 27  |  Issue : 2  |  Page : 178-183
Evaluation of serum uric acid levels in patients with oral squamous cell carcinoma


Department of Oral Medicine and Radiology, Al Badar Rural Dental College and Hospital, Gulbarga, Karnataka, India

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Date of Submission29-Jan-2015
Date of Decision25-Mar-2016
Date of Acceptance06-Apr-2016
Date of Web Publication30-May-2016
 

   Abstract 


Background: Worldwide, oral carcinoma is one of the most prevalent cancers and is one of the most common causes of death. Toxicity by oxygen radicals has been suggested as an important cause of cancer. Several researchers have reported an association of plasma/serum uric acid with different cancers.
Aim: The aim was to determine the serum uric acid level in patients with newly diagnosed oral squamous cell carcinoma (OSCC) and then to compare and correlate it with those of normal subjects and also to determine the role of uric acid in the etiology of OSCC.
Materials and Methods: The study group included 41 OSCC patients and 40 age- and sex- matched healthy subjects as a control group. Estimation of serum urate concentration was determined enzymatically with a commercially available reagent. The data were statistically evaluated with Student's t-test and Chi-square test using SPSS 11.5 software.
Results: The mean serum uric acid levels were very low with the study group as compared to control group and were very highly significant (t = 4.14, P < 0.001). It was also found that risk of OSCC was more in a study group with low serum uric acid levels with tobacco intake.
Conclusion: This study showed that serum uric acid was lower in oral cancer patients compared with healthy volunteers and low serum uric acid was associated with increased risk of oral cancer development.

Keywords: Antioxidant, oral cancer, serum uric acid

How to cite this article:
Ara SA, Ashraf S, Patil BM. Evaluation of serum uric acid levels in patients with oral squamous cell carcinoma. Indian J Dent Res 2016;27:178-83

How to cite this URL:
Ara SA, Ashraf S, Patil BM. Evaluation of serum uric acid levels in patients with oral squamous cell carcinoma. Indian J Dent Res [serial online] 2016 [cited 2020 Feb 22];27:178-83. Available from: http://www.ijdr.in/text.asp?2016/27/2/178/183128


Oral cancer includes a group of neoplasms affecting any region of the oral cavity, pharyngeal regions, and salivary glands. However, this term tends to be used interchangeably with oral squamous cell carcinoma (OSCC), which represents the most frequent of all oral neoplasms. It is estimated that more of 90% of all oral neoplasms are OSCC.[1]

Worldwide, oral cancer accounts for 2–4% of all cancer cases. In some regions, the prevalence of oral cancer is higher, reaching around 45% of all cancers in India and 10% in Pakistan.[1]

Toxicity by oxygen radicals has been suggested as an important cause of cancer. Oxygen radicals and other oxidants are toxic mainly because of their ability to initiate the chain reaction of lipid peroxidation. Lipid peroxidation, in turn, generates reactive species such as radicals, hydroperoxides, aldehydes, and epoxides with the capability of causing cellular, DNA, and RNA injuries.[2]

Epidemiological studies have revealed that low levels of essential antioxidants in circulation are associated with an increased risk of cancer.[3] The possible protective action of many of the natural antioxidants that are found in biological fluids and tissues has been the subject of intense investigation.[4] These protective mechanisms are now recognized as anti-carcinogenic and even having the ability to increase lifespan.[5] Recent findings suggest that examination of specific cancers in relation to serum uric acid levels may be worthwhile.[4]

Uric acid has been demonstrated to be an important antioxidant and a free radical scavenger in humans. It is one of the major radical-trapping antioxidants in plasma and is reported to protect the erythrocyte membrane against lipid peroxidation. Uric acid interacts with peroxynitrite to form a stable nitric oxide donor, thus promoting vasodilatation and reducing the potential for peroxynitrite-induced oxidative damage. Thus, uric acid could be expected to protect against oxidative stresses.[3]

Usefulness of variation in tissues/blood uric acid levels in diagnosis and treatment of various diseases has been studied by several workers. It is also possible that the effect of serum uric acid on etiology of cancer may vary from one type of cancer to another; low serum uric acid may be associated with increased risk of lung and oral cancer for instance while high serum uric acid may be associated with increased risk of other types of cancer.[2]

It is therefore important to identify new diagnostic and predictive approaches. In the recent years, emphasis has been placed on detecting molecular markers from body fluid, such as saliva, urine, and others, for detecting cancer, predicting prognosis, and monitoring disease prognosis. The idea of screening and following patients with malignancy by blood-based tests is appealing from several points of view including its ease, economic advantage, noninvasiveness, and possibility of repeated sampling. Several researchers have reported an association of plasma/serum uric acid with different cancers; however, to the best of our knowledge, this is the second study to report the association of plasma/serum uric acid in head and neck cancers. Hence, the study was undertaken to evaluate serum uric acid in oral cancer patients. Further, this study also compared and correlated the possible role of serum uric acid in oral cancer etiopathogenesis.


   Materials and Methods Top


The study was conducted in the Department of Oral Medicine and Radiology of Al-Badar Rural Dental College and Hospital, Gulbarga, Karnataka.

The subjects were from the patients attending the outpatient Department of Oral Medicine and Radiology. The study included a total of 81 subjects, 41 patients with OSCC in the experimental group and 40 patients in control group.

The study was conducted by strictly adhering to the ethical protocols, and written consent was obtained from all the patients to include them in the study.

Inclusion criteria

  • Group I: Forty-one patients of oral cancer based on the selection criteria were included in the study
  • Group II: Control group consisted of age- and sex-matched forty healthy subjects with no oral cancer and no known systemic diseases that affect serum uric acid levels.


Exclusion criteria

  1. In all groups, individuals suffering from known systemic diseases such as gout, renal diseases, cardiovascular disease, and diabetes
  2. Patients who are on medications that might affect serum uric acid levels
  3. Patients with other malignancies except OSCCs
  4. Patients undergoing treatment for OSCC.


Two milliliters of intravenous blood was taken from all participants after an overnight fast. The blood was centrifuged at 3000 rpm for 5 min and separated serum was aspirated into tubes and analyzed for uric acid using the reagent kit and BTS 350 Semi-Auto analyzer [BioSystems S.A. Costa Brava, Barcelona (Spain)].

Tabulation of the results was carried out for oral cancer and the control group. All the variables from the study were statistically analyzed for the mean values, standard deviation, and “P” value. Multiple group comparisons were done by ANOVA. Evaluation of results and statistical analysis were carried out using Student's t-test and Chi-square test. For all tests, P values ≤ 0.05 were utilized for statistical significance.


   Results Top


All the subjects were in the age range of 21–80 years. The result showed (χ2 = 0.448, P > 0.05) no statistically significant difference in the distribution of age among study and control group [Graph 1].



The mean age among study group was 53.2 ± 16.8 and that of the control group was 52.02 ± 14.63. The comparison of this shows no statistical significance (t = 0.25, P > 0.05) [Table 1].
Table 1: Mean age-wise comparison of study and control group

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The male to female ratio of the study group was 1.4:1 and that of the control group was 1.35:1. The distribution of sex among the study and control group had no statistical significance and was same (χ2 = 0.0089, P > 0.05) [Table 2].
Table 2: Gender-wise distribution of cases

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The buccal mucosa was the most common involved site followed by the vestibule [Graph 2].



Habit

Of 41 study group, 30 (85.7%) patients had only tobacco intake (in any form) as habit and 9 (81.8%) patients consumed tobacco and alcohol. Among forty control subjects, only 5 (14.3%) had tobacco (in any form) as habit and 2 (18.2%) subjects had tobacco and alcohol. The result showed a very high significance with subjects taking only tobacco (χ2 = 30.37, P <</i> 0.001). Subjects with a habit of consuming both tobacco and alcohol showed a significant result (χ2 = 4.95, P <</i> 0.05) [Graph 3].



Serum uric acid levels

In the study group, out of 41 patients, 13 (31.7%) patients had low serum uric acid levels (<3 mg/dl), 26 (63.4%) patients had normal serum uric acid levels (3–6 mg/dl) and 2 (4.9%) patients had high serum uric acid levels (>6 mg/dl). Among 40 subjects in control group, 3 (7.5%) subjects had low serum uric acid levels (<3 mg/dl), 20 (50.0%) subjects had normal serum uric acid levels (3–6 mg/dl), and 17 (42.5%) subjects had high serum uric acid levels (>6 mg/dl). The distribution of serum uric acid levels among the study group and the control group showed statistically very high significance (
χ2 = 18.86, P < 0.001) [Table 3].
Table 3: Serum uric acid levels in study group and control group

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Comparison of mean uric acid among study group and control group

Among 41 study group, the mean serum uric acid was 3.80 ± 2.26. The mean serum uric acid among 40 control group was 5.66 ± 1.82. The mean serum uric acid in the study group was very low when compared to the control group. Statistically it showed very highly significance (t = 4.14, P < 0.001). This shows that the low serum uric acid was associated with the increased risk of OSCC [Table 4].
Table 4: Comparison of mean uric acid among study group and control group

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Comparison of risk factors for oral squamous cell carcinoma

Among the 41 study group and 40 control group, there were 13 (31.7%) patients and 3 (7.5%) subjects with low serum uric acid, respectively. This is statistically highly significant (χ2 = 7.48, P > 0.0086).

Of 41 study group, 30 (85.7%) patients had only tobacco intake (in any form) as habit and 9 (81.8%) patients consumed tobacco and alcohol. Among 40 control subjects, only 5 (14.3%) had tobacco (in any form) as habit and 2 (18.2%) subjects had tobacco and alcohol. The result showed a very high significance with subjects taking only tobacco (χ2 = 30.37, P< 0.001). Subjects with a habit of consuming both tobacco and alcohol showed a statistically significant result (χ2 = 4.95, P <</i> 0.05).

The study group with OSCC showed low serum uric acid levels and tobacco intake (in any form) when compared to control group. It showed a very high statistical significance (
χ2 = 30.37, P < 0.001) [Table 5].
Table 5: Comparison of risk factors for oral squamous cell carcinoma

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   Discussion Top


OSCC is a major health problem worldwide. It is among the most common cancers seen in both Indian men and women as can be gauged from the records of the National Cancer Registry Programme.[6]

Toxicity by oxygen radicals has been suggested as a major cause of cancer, heart disease, and aging. Aerobic organisms have an array of protective mechanisms now being recognized as anti-carcinogenic and in some cases, even as life-span extending. Ames et al. proposed that the uric acid may act to prevent the formation of oxygen radicals and thereby protect against carcinogenesis.[7]

Only few studies have tested the association between uric acid and carcinogenesis with inconsistent results.[2] Mazza et al.,[8] in a study in Italy, found that serum uric acid could protect against cancer. This was corroborated by Bozkir et al.[9] who reported a significantly lower serum uric acid in lung cancer patients compared to healthy controls.

The increased risk of cancer mortality obtained in some of these studies may be due to the markedly high serum uric acid observed in some cancer patients, which may be attributed to the malignant process itself, resulting from the increased nucleic acid turnover in the rapidly proliferating diseased tissue.[10]

Lawal et al.[2] have examined the role of uric acid in the etiology of oral cancer, and found that serum uric acid level was lower in oral cancer patients compared to the control group probably due to nutritional compromise as a result of tumor necrosis factor and interleukin-6 being produced in these patients, which causes loss of appetite.[11]

Our study consists of 81 samples. 41 patients of oral cancer based on the selection criteria were included in the study. The control group consisted of age- and sex-matched 40 healthy subjects with no oral cancer and no known systemic diseases that affect serum uric acid levels.

Age

In our study, 41 patients were in the age range of 21–80 years with the mean age of 53.2 ± 16.8 years. This is comparable to the mean age of 49.73 years specified by Shenoi et al.[12]

Majority of our cases which were 12 (29.3%) in number were in the age range of 41–50 years. Thus, most of our patients were in the fourth and fifth decades of life. This is in agreement with Sankaranarayanan et al.[13] where they found that the peak age frequency of occurrence (the fifth decade of life) in India is at least a decade earlier than that described in the western literature.

Sex

In our study, among 41 OSCC patients, 24 (58.5%) were males and 17 (41.5%) were females, thus showing a male predominance with a male to female ratio of 1.4:1. Similar male predominance was reported by Shenoi et al.[12] (4.18:1), higher than that reported in most studies. However, the highest male predominance with OSCC was reported for the study conducted in a Greek population [14] with a male to female ratio of 9.2:1.

Site of oral cancer

With regard to the site distribution in our study, the buccal mucosa was the most common involved site with all the 28 (68.3%). Vestibule was the second most common site and affected 13 (31.7%) of patients. This is followed by retromolar area in 10 (24.4%) patients, tongue in 7 (17.1%) patients, palate in 6 (14.6%) patients, alveolus in 5 (12.2%) patients, floor of the mouth in 4 (9.7%), and lips in 3 (7.3%) of patients. Our findings are consistent with studies by Sherin et al.[6] and Sankaranarayanan et al.[13] in the Indian population for increased incidence of oral cancer involving buccal mucosa.

Habit

Of 41 OSCC patients in this study, 30 (85.7%) patients had only tobacco intake (in any form) as habit and 9 (81.8%) patients consumed tobacco and alcohol. Among 40 control subjects, only 5 (14.3%) had tobacco (in any form) as habit and 2 (18.2%) subjects had tobacco and alcohol. A very high significance was noticed with subjects taking only tobacco. A significant result was also noted with subjects consuming both tobacco and alcohol. The Indian data suggest that the relative risk of developing oral cancer is 2.82 for smokers and 5.98 for chewers.[15] Sanghvi et al. observed that the risk ratios for oral cancers were four-fold in chewers, two-fold in smokers, and four-fold in chewers and smokers both.[12]

Comparison of mean uric acid among study group and control group

In our study, the mean serum uric acid in the study group was very low when compared to the control group. Statistically it showed very high significance. This is comparable to the studies done by Lawal et al.,[2]Abiaka et al.,[16] and Nagini et al.[17] where they found a significant difference in low serum uric acid associated with increased risk of oral cancer compared to healthy subjects.

Comparison of serum uric acid as risk factor for oral squamous cell carcinoma

In this study, among the 41 study group and 40 control group there were 13 (31.7%) patients and 3 (7.5%) subjects with low serum uric acid, respectively. This was statistically highly significant. Of 41 study group, 30 (85.7%) patients had only tobacco intake (in any form) as habit and 9 (81.8%) patients consumed tobacco and alcohol. Among 40 control subjects, only 5 (14.3%) had tobacco (in any form) as habit and 2 (18.2%) subjects had tobacco and alcohol. The result showed a very high significance with subjects taking only tobacco. Subjects with a habit of consuming both tobacco and alcohol showed a statistically significant result.

According to Abiaka et al.,[16] depleted serum urate in smokers in comparison to nonsmokers in the patient group may indicate more deleterious consequences for the smokers which is in agreement with our study as well as other studies such as Hanna et al.,[18] Alberg,[19] van der Vaart et al.,[20] Polidori et al.,[21] Maxwell and Bruinsma,[22] Boon et al.,[23] Dietrich et al.,[24] and Goraca and Skibska [25] that showed low serum uric acid in regular smokers and reduction of antioxidants including uric acid in smokers, indicating that oxidative stress increases every time a cigarette is smoked.[18]

The development of cancer is multifactorial, depending on the extent of DNA damage that is proportional to the magnitude of oxidative and nitrative stress. This stress reflects the net effect of both reactive oxygen species (ROS) and reactive nitrogen species (RNS) on the one hand and the effectiveness of antioxidant defense and the DNA repair systems on the other. In fact, it has been found that, whereas ROS and RNS are involved in the initiation and promotion of multistep carcinogenesis, both are inhibited by antioxidants. However, when the equilibrium is broken either by a reduction in the levels of antioxidants or by enhancement of ROS and RNS levels, DNA is oxidized, and cancer evolves.[13],[21] Hence the findings from our study and the literature review strongly warrant an in-depth study of alterations in serum uric acid in OSCC patients.


   Conclusion Top


Toxicity by oxygen radicals has been suggested as an important cause of cancer. Uric acid has been demonstrated to be an important antioxidant and a free radical scavenger in humans. It is one of the major radical-trapping antioxidants in plasma and is reported to protect the erythrocyte membrane against lipid peroxidation.

This study showed that serum uric acid was lower in oral cancer patients when compared with healthy volunteers and low serum uric acid was associated with increased risk of oral cancer development.

This study does not entirely resolve the controversy of the role of serum uric acid in cancer etiology. Further prospective cohort studies with an extensive sample size are suggested to substantiate the results as well as to better understand the role of serum uric acid in etiology of oral cancer.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

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Markopoulos AK. Current aspects on oral squamous cell carcinoma. Open Dent J 2012;6:126-30.  Back to cited text no. 1
    
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Correspondence Address:
Syeda Arshiya Ara
Department of Oral Medicine and Radiology, Al Badar Rural Dental College and Hospital, Gulbarga, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9290.183128

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