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ORIGINAL ARTICLE
Year : 2012  |  Volume : 8  |  Issue : 3  |  Page : 384-388

Serum lipid profile in oral cancer and leukoplakia: Correlation with tobacco abuse and histological grading


1 Department of Oral and Maxillofacial Pathology, Maulana Azad Institute of Dental Sciences, New Delhi, India
2 Department of Oral Medicine and Radiology, Maulana Azad Institute of Dental Sciences, New Delhi, India
3 Department of Public Health Dentistry, Maulana Azad Institute of Dental Sciences, New Delhi, India

Date of Web Publication17-Nov-2012

Correspondence Address:
Priya Kumar
Department of Oral and Maxillofacial Pathology, Maulana Azad Institute of Dental Sciences, Bahadur Shah Zafar Marg, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.103517

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 > Abstract 

Introduction: Role of alterations in serum lipid profile in oral cancer remains controversial. The present study aimed to evaluate the implications of altered serum lipid profile in patients with oral cancer (OC), oral leukoplakia (OLP), and tobacco habits.
Materials and Methods: Thirty patients with OC, 30 with OLP, 30 tobacco abusers (TAs), and 30 age and sex matched healthy controls were included in the study. Serum lipid profile including total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), Very low density lipoprotein (VLDL), and triglycerides (Tg) were evaluated using a fully automatic Biochemistry analyzer. Difference in lipid profile in various types of TA, that is, smokeless tobacco (SLT), smoking tobacco (ST), and a combination (Comb) usage of both forms were also analyzed.
Results: TC, HDL, and LDL were much lower in the OC group compared with control. Although these parameters were low in the OPC group compared with controls, the difference was not significant. On histological analysis, TC and HDL were found to decrease marginally with loss of tumor differentiation in OC. No correlation was found between the mean serum lipid profiles and degree of dysplasia in OLP. TC and HDL were significantly lesser in all forms of TA when compared with control.
Conclusions: There may be an inverse relationship between serum lipid profile and OC. No significant reduction in lipid profile was observed in the OLP group. This may indicate that hypolipidemia is a late change occurring during carcinogenesis or is an effect rather than the cause of cancer.

Keywords: Leukoplakia, oral cancer, serum lipid profile, tobacco abuse


How to cite this article:
Kumar P, Augustine J, Urs AB, Arora S, Gupta S, Mohanty VR. Serum lipid profile in oral cancer and leukoplakia: Correlation with tobacco abuse and histological grading. J Can Res Ther 2012;8:384-8

How to cite this URL:
Kumar P, Augustine J, Urs AB, Arora S, Gupta S, Mohanty VR. Serum lipid profile in oral cancer and leukoplakia: Correlation with tobacco abuse and histological grading. J Can Res Ther [serial online] 2012 [cited 2019 Nov 12];8:384-8. Available from: http://www.cancerjournal.net/text.asp?2012/8/3/384/103517


 > Introduction Top


Oral cancer (OC) is the leading cause of morbidity and mortality due to cancer in India and is most commonly preceded by clinically definable premalignant lesions and conditions. Around 0.3-25% of leukoplakias and 7-12% of oral submucous fibrosis cases will undergo malignant transformation. [1],[2]

Early detection of these lesions can dramatically improve the treatment outcome and prognosis in such patients. Carcinoma development is a complex mechanism comprising of proliferation, apoptosis and differentiation and the interplay between these intricate processes decides tumor development and progression. [3] Thus, the development of newer diagnostic and predictive approaches that are safe, economical, and amenable to repeated sampling is imperative. Blood-based/serum-based tests offer the aforementioned advantages.

Fundamentally, the newly proliferating tumor cells would need many basic components well above the normal limits, used in physiological process. One such component is lipids which form major cell membrane components essential for various biological functions including cell division and growth of normal and malignant tissues. The increased requirement of lipids to fulfill the need of these new cells would be expected to diminish the existing lipid stores. Altered lipid levels have been consistently associated with coronary heart disease and their relation to different cancers such as breast and colorectal have also been documented. [4],[5] However, the reports on altered lipid levels in OC and precancer are few and conflicting.

With the above in mind, the present study was conducted to evaluate the implications of altered serum lipid profile in patients with OC, oral leukoplakia (OLP), and tobacco habits. An attempt was made to compare and correlate serum lipid profile with histological grading in patients of OC and OLP. The difference in lipid profile patterns in smokeless tobacco (SLT) and smoking tobacco (ST) abusers was also studied.


 > Materials and Methods Top


A total of 120 subjects ranging in age from 20 to 60 years, were included in the prospective study that was approved by the ethical committee of the institute. The subjects were divided into the following four groups. Group I consisted of 30 histopathologically diagnosed cases of OC. These patients were graded histologically into well differentiated, moderately differentiated, and poorly differentiated carcinomas. Group II consisted of 30 cases of OLP. These lesions were biopsied and then examined for the presence or absence of dysplasia. When present, dysplasia was graded into mild, moderate, and severe dysplasia. All histological grading was performed independently by two different pathologists to remove any subjective bias. Group III consisted of 30 subjects indulging in some form of tobacco abuse (TA) but without any clinically evident oral lesions. This group was subdivided further depending on the use of SLT, ST, or a combination (Comb) of both forms. Group IV comprised 30 age and sex matched healthy controls without any history of tobacco abuseTA and without any evident oral lesions.

Patients who were obese (with a body mass index (BMI) above the recommended range), known cardiac patients, renal patients, patients suffering from some form of liver disease, diabetics, thyroid disorders, or those undergoing treatment for oral carcinoma were excluded from the study.

After obtaining informed written consent from the participating patients, a thorough clinical history including the height and weight (to calculate BMI); type, form, frequency, and duration of TA were taken. Meticulous clinical examination was then performed.

Analysis of lipid profile

A 5-ml of fasting (12-14 hours.) blood sample was collected under sterile conditions in plain vacutainer and allowed to clot for 1 hour. The vacutainer was centrifuged at 3000 rpm for 5 minutes. Serum was then analyzed for lipid profile including total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), and triglycerides (Tg). Fully automatic biochemistry analyzer (Erba EM 360, Mannheim® , Germany) based on the principle of photometry was used to carry out the lipid analysis.

Statistical analysis

The results obtained after tabulation were analyzed using the SPSS Version 16 software (Statistical Package for Social Sciences, Gainesville, FL, USA). Mean values along with standard deviation were calculated for all values under consideration. Analysis of variance (ANOVA) was used to compare the lipid profile variables between various groups with various grades of carcinoma and dysplasia. Student's t-test was used to compare between different forms of TA.


 > Results Top


Out of the 120 patients examined for the study, there were 106 males and 14 females. The distribution of male and female subjects between the four groups is elaborated in [Table 1]. The age of patients examined varied from 20 to 60 years with most of the patients in the fourth and fifth decades of life [Table 1].
Table 1: Age and sex distribution of subjects across various groups

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Mean serum lipid profile in oral cancer, oral leukoplakia, tobacco abusers without lesions and controls

The mean serum lipid profile of all patients was analyzed and is summarized in [Table 2]. The TC, HDL, and LDL values were found to decrease progressively as one moved from the control group to that of TAs, OLP, and OC group [Figure 1]. A statistically significant reduction (P < 0.05) was noted only between the OC and control group. Although serum Tg was much lesser in OC group as compared with control group, the results were not significant statistically. A statistically significant reduction in serum HDL and LDL was noted between the OC and OLP group.
Figure 1: Distribution of mean serum lipid profi le across various groups

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Table 2: Distribution of mean serum lipid profi le across all groups and statistical comparison of P values across groups

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Histologically, OC group was graded as well, moderately and poorly differentiated. A total of 21 cases of well differentiated, 7 of moderately differentiated, and 2 of poorly differentiated oral squmaous cell carcinomas were identified. Although, serum TC and HDL were found to decrease marginally with loss of tumor differentiation, the finding was not significant statistically. All other parameters, that is, LDL, VLDL, and Tg showed no correlation with the grade of tumor differentiation [Figure 2].
Figure 2: Mean serum lipid profile in different histological grades of OC

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OLP group was graded histologically as having no dysplasia (n = 21), mild dysplasia (n = 7), moderate dysplasia (n = 2), and severe dysplasia (n = 0). No correlation was found between the mean serum lipid profiles and degree of dysplasia observed [Figure 3]. The findings have been summarized in [Table 3].
Figure 3: Mean serum lipid profile in different histological grades of OPC

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Table 3: Distribution of serum lipid profi le in 60 subjects according to histopathological grading

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Mean serum lipid profile in different forms of tobacco abuse

Tobacco habits of the cases studied were analyzed and divided into SLT, ST, and a Comb of both SLT and ST. SLT use was in the form of gutkha, tobacco quid, pan with tobacco, and snuff. Bidi and cigarette were the two forms of ST encountered. None of the patients with oral squamous cell carcinoma or OLP were without a tobacco habit.

In the 30 cases diagnosed clinically and histologically as oral squamous cell carcinoma, 18 were abusers of SLT, 8 were smokers, and 4 used combination of both forms. In the 30 cases identified as leukoplakia, 13 were SLT users, 12 ST users and 5 used combination of both forms. When the habits of TAs without any clinically evident lesions, for whom biopsy was not performed were studied, the number of cases for SLT, ST, and Comb were 14, 12, and 4, respectively.

When the mean serum lipid profile was compared between the above three groups, a minor decrease in all parameters was seen in the SLT group as compared with the ST and SLT+ST group. A statistically significant decrease in TC and HDL was seen in the SLT and ST group when compared with control group. There was no statistically significant correlation between the other variables and the various groups studied. VLDL was more in the control group as compared with the other three groups [Figure 4], [Table 4].
Figure 4: Mean serum lipid profile in different forms of tobacco abuse

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Table 4: Distribution of mean serum lipid profi le in different forms of tobacco abuse and their statistical P value comparisons

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 > Discussion Top


Cholesterol can be obtained either from the diet or may be synthesized by the body. Lipoprotein particles are responsible for the transport of cholesterol and lipids in the circulation. Tg derived from the gut are transported by chylomicrons, whereas VLDL and LDL particles distribute liver-derived Tg and cholesterol to peripheral tissues. HDL particles transport excess cholesterol from the periphery to the liver for excretion. [6]

The detailed study of cholesterol carrying lipoprotein transport and the efficiency of the receptor system may thus help in understanding the underlying mechanisms of regulation of serum cholesterol concentrations in cancer.

Data collected from studies that relate dyslipidemias with cancer development remain conflicting. It has been proposed that hypolipidemia is a predisposing factor for cancer development although no causative relation has been established so far. However, some authors believe that hypolipidemia is the result rather than the cause of cancer. [7]

Possible hypotheses for hypolipidemia in cancer and precancer

Current theories regarding cancer causation have generated interest in variables such as levels of serum cholesterol and Tg as potential associations with cancer relating to dietary factors or basic constitutional factors.

  • Newly forming and rapidly proliferating malignant cells need many basic components such as lipids well above the normal physiological limits leading to diminished lipid stores.
  • Tobacco induces generation of free radicals and reactive oxygen species responsible for high rate of oxidation/peroxidation of polyunsaturated fatty acids (PUFA), in turn leading to increased utilization of lipids.
  • Lower cholesterol levels before detection of carcinoma may be due to underlying carcinoma process.
  • Association of hypolipidemia with cancer may be secondary to other factors.
  • May be due to increased membrane permeability to carcinogens induced by trans fatty acids.
  • May be due to antioxidant vitamin therapy. [8],[9]
  • Lipid peroxidation may play an important role in cancer development as lipid peroxidation product, malondialdehyde, may cross-link deoxyribonucleic acid (DNA) on the same and opposite strands via adenine and cytosine. This may in theory contribute to carcinogenecity and mutagenecity in mammalian cells. [10] Lipid peroxidation may be induced by tobacco carcinogens that are known to produce reactive oxygen species and lipid peroxides.


The results of the present study show that TC, HDL, and LDL were significantly reduced in the OC group when compared with the control group. Lohe et al. and Patel et al. found a significant decrease in TC, HDL, VLDL, and Tg but not in LDL in patients with oral squamous cell carcinoma when compared with the control group. [8],[11] Chawda et al. found significantly lower serum TC, HDL, and Tg in patients with oral squamous cell carcinoma. [12] Since LDL-cholesterol is more susceptible to oxidation in various pathologic conditions, its higher peroxidation occurs during oxidative stress as compared with HDL, which prevents the generation of free radicals responsible for lipid peroxidation. [13]

Blood cholesterol is believed to undergo significant changes early on in the process of carcinogenesis. [14] Since oral squamous cell carcinoma is more often than not preceded by oral precancerous lesions, an attempt was made to analyze the serum lipid levels in oral precancers as well. In comparison to controls, the levels of TC, HDL, and LDL were lower in the OPC group but the results were not significant statistically. However, other studies have found a significantly lower level of TC and HDL in oral precancer. [8],[11] Mehrotra et al. and Nayak et al. found significantly lower level of TC and HDL in oral submucous fibrosis, a premalignant condition, when compared with controls. [15],[16] A marked decrease in serum LDL (P < 0.005) and HDL (P < 0.027) was seen in the OC group when compared with the OPC group in our study. This is in concurrence with the findings of Lohe et al. and may indicate overutilization of lipids during transformation from oral precancer to cancer. [8]

The OC group was studied histologically and graded into well, moderately, and poorly differentiated carcinomas according to the degree of differentiation. Although, serum TC and HDL decreased with the loss of differentiation, the findings were insignificant statistically. Additionally, no correlation could be found between the dysplasia grade in OLP and serum lipid profile. Similar findings were observed in the study of Lohe et al. who found no correlation between histological grading and serum lipid profile in OC and precancer. [8]

All cases of OC and OPC analyzed in the present study had a tobacco habit. As previously described, the tobacco habituates were divided into abusers of SLT, ST, and a combination of both forms. The serum lipid levels of were analyzed in all forms of TA. A statistically significant reduction in TC and HDL was observed when compared with the control group. Our findings correlate well with those of other studies that also show similar findings. [8],[11] Moreover, the levels of all five parameters were much lesser in the SLT group as compared with the ST group. This could be because SLT is associated with significantly greater deleterious cardiovascular effects due to larger overall exposure owing to prolonged absorption. [17]

However, finding with respect to SLT use have shown variable results in different studies. In a study of 2840 adult men, SLT users had two and a half times the adjusted risk of hypercholesterolemia compared with nonusers. In another study, involving 90 patients from India, SLT users had lower HDL but higher Tg levels when compared with nonusers. [18],[19]

To conclude, there seems to be an inverse relationship between serum lipid profile and cancer. Serum TC, HDL, and LDL were significantly less in OC patients when compared with controls. No significant reduction in lipid profile was observed in the precancer group. This may indicate that hypolipidemia is a late change occurring during carcinogenesis or is an effect rather than the cause of cancer. No significant correlation exists between the degree of differentiation in carcinoma, degree of dysplasia in leukoplakia and the serum lipid profile. Tobacco habituates in all forms (SLT and ST) have lower serum lipid levels than non TAs. Moreover, all forms of TA seem to be deleterious. Analysis of lipid profile in a greater number of oral precancer and cancer patients may further strengthen this hypothesis of an inverse relationship between OC and hypolipidemia.

 
 > References Top

1.Hazarey VK, Erlewad DM, Mundhe KA, Ughade SN. Oral submucous fibrosis: Study of 1000 cases from central India. J Oral Pathol Med 2007;36:12-7.  Back to cited text no. 1
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2.Napier SS, Speight PM. Natural history of potentially malignant oral lesions and conditions: An overview of the literature. J Oral Pathol Med 2008;37:1-10.  Back to cited text no. 2
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3.Cheng B, Rhodus NL, Williams BA, Griffin RJ. Detection of apoptotic cells in whole saliva of patients with oral premalignant and malignant lesions: A preliminary study. J Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;97:465-70.  Back to cited text no. 3
    
4.Gerber M, Cavallo F, Marubini E, Richardson S, Barbieri A, Capitelli E, et al. Liposoluble vitamins and lipid parameters in breast cancer. A joint study in northern Italy and southern France. Int J Cancer 1988;42:89-94.  Back to cited text no. 4
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5.Forones NM, Falcao JB, Mattos D, Barone B. Cholesterolemia in colorectal cancer. Hepatogastroenterology 1998;45:1531-4.  Back to cited text no. 5
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6.Otis JP, Sahoo D, Drover VA, Yen CE, Carey HV. Cholesterol and lipoprotein dynamics in a hibernating mammal. PLoS One 2011; 6:e29111.  Back to cited text no. 6
    
7.Raste AS, Naik PP. Clinical significance of lipid profile in cancer patients. Indian J Med Sci 2000;54:435-41.  Back to cited text no. 7
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9.Bielecka-Dbrowa A, Hannam S, Rysz J, Banach M. Malignancy-Associated Dyslipidemia. Open Cardiovasc Med J 2011;5:35-40.  Back to cited text no. 9
    
10.Marnett LJ, Tuttle MA. Comparison of the mutagenecity of malondialdehyde and the side-products formed during its chemical synthesis. Cancer Res 1980;40:276-82.  Back to cited text no. 10
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11.Patel PS, Shah MH, Jha FP, Raval GN, Rawal RM, Patel MM, et al. Alterations in plasma lipid profile patterns in head and neck cancer and oral precancerous conditions. Indian J Cancer 2004; 41:25-31.  Back to cited text no. 11
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12.Chawda JG, Jain SS, Patel HR, Chaduvula N, Patel K. The relationship between serum lipid levels and the risk of oral cancer. Indian J Med Paediatr Oncol 2011;32:34-7.  Back to cited text no. 12
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13.Regnstrom J, Nisson J, Toruvall P, Laudou C, Hamsten A. Susceptibility to low-density lipoproteins oxidation and coronary atherosclerosis in man. Lancet 1992;339:1883-6.  Back to cited text no. 13
    
14.Alexopoulos CG, Blastios B, Avgerinos A. Serum lipids and lipoprotein disorders in cancer patients. Cancer 1987;60:3065-70.  Back to cited text no. 14
    
15.Mehrotra R, Pandya S, Chaudhary AK, Singh HP, Jaiswal RK, Singh M, et al. Lipid profile in oral submucous fibrosis. Lipids Health Dis 2009;8:29.  Back to cited text no. 15
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17.Pais P, Fay MP, Yusuf S. Increased risk of acute myocardial infarction associated with bidi and cigarette smoking in Indians: Final report on tobacco risks from a case - control study. Indian Heart J 2001;53:731-5.  Back to cited text no. 17
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


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