|Year : 2020 | Volume
| Issue : 4 | Page : 187-191
A comparative study to assess the independency of lipid profile and blood sugar levels as a diagnostic marker in oral cancer and precancerous disorders
Rohan Sachdev1, Kriti Garg2, Garima Singh3, Vishal Mehrotra2
1 UWA School of Population and Global Health, University of Western Australia, Nedlands, Western Australia, Australia
2 Department of Oral Medicine and Radiology, Rama Dental College, Kanpur, Uttar Pradesh, India
3 Department of Pedodontics, Rama Dental College, Kanpur, Uttar Pradesh, India
|Date of Submission||14-Nov-2019|
|Date of Decision||28-Aug-2020|
|Date of Acceptance||18-Sep-2020|
|Date of Web Publication||13-Oct-2020|
UWA School of Population and Global Health, University of Western Australia, Nedlands, Western Australia
Source of Support: None, Conflict of Interest: None
Context: Lipids are the main cell membrane components important for different biological functions including cell growth and division of normal and malignant tissues. Low lipid values in cancer, precancer lesion, and condition may be due to of lipid peroxidation and also lipids play a key role in the higher utilization of lipids including total cholesterol (TC) and triglycerides (TG) for new membrane biogenesis. Aims: The present study was aimed to assess the independency and comparison of serum lipid profile and blood glucose level in patients with oral carcinoma and precancerous lesions and conditions. Settings and Design: The total sample sizes of 180 individuals were chosen in a 2-year duration: 60 were diagnosed with leukoplakia/oral submucous fibrosis, 60 with oral carcinoma, and 60 of the control group. Subjects and Methods: The serum triglycerides (TGs) were estimated by GPO-PAP End Point Assay method, total cholesterol (TC) by CHOD-PAP, and high-density lipoprotein (HDL) cholesterol by PEG-CHOD-PAP End Point Assay method with lipid clearing factors. The low-density lipoprotein (LDL) and very LDL (VLDL) levels were calculated using Friedewald's equation. Statistical Analysis Used: Collected data were statistically calculated by Student's t-test and by Chi-square test with SPSS version 17. All values were considered statistically significant for a value of P < 0.05. Results: This study showed that parameters TC, TG, and HDL of lipid profile were reduced in the oral precancerous study group as compared to the oral carcinoma study group, whereas in all the study groups, no statistically changes were found in LDL, VLDL, fasting blood sugar, and postprandial blood sugar levels. Conclusions: Low serum value of TC, TG, and HDL may be the indicator for the increased risk of developing precancer diseases and oral cancer in healthy individuals with tobacco habits. Low lipid profile parameters can be used as diagnostic markers in assessment of oral cancer and precancer along with other parameters of biochemical markers.
Keywords: Blood sugar, oral cancer, precancerous lesions, total cholesterol, triglycerides
|How to cite this article:|
Sachdev R, Garg K, Singh G, Mehrotra V. A comparative study to assess the independency of lipid profile and blood sugar levels as a diagnostic marker in oral cancer and precancerous disorders. Indian J Dent Sci 2020;12:187-91
|How to cite this URL:|
Sachdev R, Garg K, Singh G, Mehrotra V. A comparative study to assess the independency of lipid profile and blood sugar levels as a diagnostic marker in oral cancer and precancerous disorders. Indian J Dent Sci [serial online] 2020 [cited 2022 May 17];12:187-91. Available from: http://www.ijds.in/text.asp?2020/12/4/187/298027
| Introduction|| |
A biomarker can be defined as “A substance that is measured objectively and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”,,, Lipids are the most important cell membrane components required for various biological functions of the human body including cell growth, stabilization of deoxyribonucleic acid helix, and division of normal and malignant tissues., Lipids are present and circulated in body fluids in the form of lipoproteins, i.e., very-low-density lipoproteins (VLDLs) which are involved in transportation of triglycerides (TGs) from the liver to other cells. Low-density lipoproteins (LDLs) are responsible for the transportation of cholesterol from the liver to the cells, and high-density lipoproteins (HDLs) are involved for the transport of cholesterol from the cells to the liver. The usefulness of variations in blood cholesterol levels helps in the diagnosis of several diseases of oral cavity like decrease in the level of cholesterol has been associated with an increased risk of oral carcinoma. Diabetes mellitus represents a group of metabolic disease and is characterized by hyperglycemia due to a total or relative lack of insulin secretion and insulin resistance or both. Progressive oral mucosa atrophy develops in diabetic patients due to a reduced rate of salivary secretion and low salivary ph, thereby raising the risk of lesions such as glossitis and cheilitis. Loss of a normal protective barrier may increase oral mucosal permeability to carcinogens.
Oral squamous cell carcinoma is often caused by specific potentially premalignant disorders, such as oral leukoplakia and oral submucous fibrosis (OSMF)., Various studies stated that there is an observed association between oral carcinoma and serum cholesterol concentrations and serum blood sugar levels in various carcinomas which may indicate a higher mortality rate in both high and low serum cholesterol concentrations., However, literatures on independency of serum lipid profiles, serum blood sugar levels, and its association with oral carcinoma are few. The present study was performed to estimate the independency and compare the lipid profile levels and blood sugar levels in patients with oral precancerous lesions/conditions, oral cancer with that of normal patients.
| Subjects and Methods|| |
The study was carried out in the department of oral medicine in a dental college, Uttar Pradesh, India. The study was reviewed and approved by the institutional ethical committee, and clearance was obtained. The study was conducted in a 2-year time period from July 2017 to August 2019.
A total sample size of 180 patients were chosen out of which 60 patients with precancerous group(Leukoplakia/OSMF), 60 with oral carcinoma group and compared with 60 control group with age and sex matched. Patients between 19 and 55 years of age who had the habit of tobacco were only included in the study. Overweight patients, patients with a family history of hyperlipidemia, patients on topical/systemic medications for leukoplakia/OSMF, patients on cytotoxic drugs or radiotherapy for oral cancer, pregnant patients, and patients taking drugs like corticosteroids were excluded from the study.
Patient's general and detailed medical, family, and personnel history was recorded, clinical examination was performed, and consent was obtained. From each patient, 5 ml of fasting (10–14 h) blood sample was collected and serum was separated. The serum TGs were estimated by GPO-PAP End Point Assay method, total cholesterol (TC) by CHOD-PAP, and HDL by PEG-CHOD-PAP End Point Assay method with lipid clearing factors. The LDL and VLDL levels were calculated using Friedewald's equation. The data collected were statistically analyzed for TC, TG, LDL, VLDL, HDL, fasting blood sugar (FBS), and postprandial blood sugar (PPBS) levels in the control patient, oral carcinoma, and leukoplakia/OSMF patient groups using Student's t-test and Chi-square test with SPSS version 21 (IBM Corp., Released 2012. IBM SPSS Statistics for Windows, version 21.0. Armonk, NY: IBM Corp. USA). All values were considered statistically significant for a value of P < 0.05.
| Results|| |
In the present study, males were more in number in each disease group as compared to females. The total number of males in each group was 78.3% of control, 88.3% of leukoplakia/OSMF, and 95% of oral carcinoma [Table 1] and Graph 1]. The mean age of the oral carcinoma group was 36.21 (range: 24–50 years), leukoplakia/OSMF group was 34.15 (range: 21–52 years), and control group was 27.03 (range: 22–55 years), and the mean difference between the control and disease groups was not statistically significant [Table 2] and [Graph 2].
|Table 2: Age-wise distribution of participants in various disease groups|
Click here to view
[Table 3] shows the comparison of mean values of lipid profile and blood sugar level in the control and leukoplakia/OSMF groups with the oral carcinoma group. The mean TC level in the control group was 165.22, oral carcinoma group was 164.05, and leukoplakia/OSMF group was 163.45. The TC value in the precancerous and oral carcinoma groups was less than the normal value but found slightly raised in the oral carcinoma group, and P value came as 0.024 for the control group, while it was 0.016 and 0.008, respectively, for the oral carcinoma and leukoplakia/OSMF groups, which was found to statistically significant (P < 0.05).
|Table 3: Comparison of mean serum lipid profile and blood sugar levels in control, leukoplakia/oral submucous fibrosis, and oral carcinoma groups|
Click here to view
The mean serum TG level in the control group was 150.65 and oral carcinoma group was 150.51, while for the leukoplakia/OSMF group, it was 147.257. The serum TG value in all the disease groups was found to be decreased than the normal value except in oral carcinoma with slightly raised values as compared to the precancerous group. The mean serum HDL level in the control group was 53.81, with P = 0.019, oral carcinoma group was 53.81, P = 0.017, and leukoplakia/OSMF group was 53.45, P = 0.005. The serum HDL cholesterol level value in all the study groups was less than the ideal value of normal individuals. For serum TG level and serum HDL, P value came statistically significant in all the disease groups (P < 0.05).
The mean serum LDL level in the control group was 65.80, oral carcinoma group was 65.73, and leukoplakia/OSMF group was 66.31. The mean serum VLDL level in the control group was 35.69, oral carcinoma group was 35.85, and leukoplakia/OSMF group was 35.62. Serum LDL cholesterol levels and VLDL in oral carcinoma and leukoplakia/OSMF were not statistically significant (P > 0.05).
The mean FBS level in the control group was 86.99, oral carcinoma group was 87.50, and Leukoplakia/OSMF was 86.70. Post-PPBS were slightly raised in all the study groups. FBS level and postprandial blood sugar levels were present with slightly raised values in all the study groups, but the difference was not statistically significant (P > 0.05).
| Discussion|| |
Despite various advances in the diagnosis and treatment modalities, there is a lack of identification of a definite cause and cure for cancer. Tobacco and areca nut are considered to be major etiological factors in various cancers, such as oral, oropharyngeal, respiratory tract, and esophageal cancers, worldwide. Squamous cell carcinoma comprises about 90%–95% of all oral malignancies, and hence, the term “oral cancer” is used in a restricted sense to describe it., Oral cancer is also considered to be occurred by various precancerous lesions and conditions. Although 2%–12% of the precancerous transform into cancers in different populations, 80% of the oral cancers progress from precancerous lesions.,
Lipids are the most important cell membrane parts that are required for various biological functions, such as maintaining cell integrity, cell growth, and division of normal and malignant cells. Changes in the lipid profiles have been observed among precancerous disease group and oral cancer group. Low levels of cholesterol in the proliferating tissues and in blood compartments could be due to the process of carcinogenesis. Lohe et al. in their study stated that serum lipid levels were inversely associated with the development of precancerous and cancerous lesions. There are three possible competing theories to explain the relation between low cholesterol and oral cancer. (a) Low cholesterol may be an indicator of cancer process even before cancer manifests clinically. (b) Low cholesterol serves as a marker for some other causal sets of variables, and its association with oral cancer may be secondary even though if it precedes cancer. (c) Low cholesterol levels may precede the development of cancer and may be causally associated with some forms of cancer. Our study had a male preponderance similar to a study by Singh et al., Mehrotra et al., and Lohe et al.,, Oral cancer occurs mainly in the older age group as suggested by Kumar et al. in their study that the fourth to fifth decade is the most common age group identified while the mean age for the precancerous disease group was 34.15 (range: 21–52 years).
In the present study, a significant decrease was noticed in mean serum cholesterol levels of lipoproteins in the oral carcinoma and leukoplakia/OSMF groups of patients as compared to the control group [Table 3]. The process of carcinogenesis reduces the levels of cholesterol in the proliferating tissues and in blood compartments. A significant decrease in serum TC level in the precancerous group when compared to the control group was observed by Lohe et al., Chawda et al., and Chalkoo et al. in their studies, which was found similar to our study results,,, while a study done by Neerupakam et al., Anand et al., and Janbaz K et al. found low levels of serum TC in oral carcinoma patients when compared with the control group, which was consistent with our study results.,,
The results of the present study showed significantly lower values in mean serum TG levels in the precancerous and oral cancer groups as compared to the control group [Table 3]. Ealla et al. and Meisel et al. have also observed a decrease in serum TG levels in the precancerous group of patients, which was found consistent with our study results., Janbaz et al. and Anand et al. found a decrease in serum TG levels in oral carcinoma patients similar to the present study results., Alexopoulos et al. have found no significant difference in serum TGs between controls and patients, while Halton et al. have observed elevated TG levels in cancer patients. Increased lipid peroxidation leads to increased breakage of cellular structural blocks such as lipids automatically leading to decreased lipid levels. The carcinogens present in tobacco and areca nut cause increased lipid peroxidation by releasing reactive oxygen species and lipid peroxides. Neufeld et al. have reported passive smoking as a significant risk factor for decreased HDLC in precancerous patients. In the present study, a significant decrease was noticed in serum HDL in the study group of patients as compared to the control group. Similar findings were reported by Mujoo et al., Anand et al., Meisel et al., and Granero Fernandez et al. in their studies to assess alterations in lipid profile levels.,,, However, in the present study, the oral carcinoma group shows a slightly higher value of total serum cholesterol, TGs, and HDLC as compared to the precancerous group of patients, which was found similar to a study by Gupta.
In the present study, serum LDL and serum VLDL levels were observed with slight variation when compared with the control group, and the difference was not statically significant similar to studies done by Mujoo et al. and Chalkoo et al., [Table 3] While Subbulakshmi et al. stated that the decrease in serum LDL and VLDL in squamous cell carcinoma cases may be due to enhanced lipid peroxidation due to decline in antioxidants, Mehrotra et al. found raised values of serum LDL and VLDL in the precancerous group of patients nonconsistent with our study results.
The result of the present study showed that FBS and PPBS levels were not changed in the precancerous (leukoplakia/OSMF) and oral cancerous groups when compared with the control group, which was consistent with the results obtained by Mujoo et al., Dikshit et al., and Saini et al.,, Meisel et al. and Albrecht et al. found that the prevalence of oral leukoplakia in diabetes is significantly high, which was inconsistent with the results of the present study., Dietrich et al. have stated that for diabetic patients, the risk of oral leukoplakia may increase to the double rate. The findings by Albrecht et al. noted that precancerous lesions often occurred in the 2nd year of diagnosed diabetes. A recent meta-analysis by Gong et al. of type 2 DM and risk for oral cancer and potentially malignant oral lesion indicated that type 2 DM poses a high risk of developing oral cancer or precancerous lesions in comparison with nondiabetic individuals, with type 2 DM exercising its main effect during the first stages of oral carcinogenesis. Various studies available stated the chance of occurrence of precancerous lesions in diabetic patients at later stage but no study as such present to correlate the relationship of oral carcinoma with blood sugar levels, similar to the present study.
The diagnostic implications of assessing lipid profile and blood sugar levels in smokers and tobacco and areca nut chewers might be that alteration in lipid profile and blood sugar levels may be the indication that the changes in the oral mucosa are occurring which may lead into premalignancy or malignancy. Similarly, changes in lipid levels if seen in precancerous patients (leukoplakia/OSMF) may alert us to further investigate using different diagnostic aids. Altered blood sugar levels may be associated with disturbed lipid metabolism; associated with inflammatory conditions of oral mucosa can turn simple dental conditions into oral carcinoma in due course of time. Thus, the estimation of lipid levels and blood sugar levels appears to be an easier and faster investigative method that should be included in routine diagnostic pathology services.
| Conclusions|| |
Oral cancers and precancers are able to metabolize lipids for their growth and to generate phospholipid membranes. Identification and characterization of more enzymes involved in these process pathways will be more imperative for the proper recording of these steps. Lipid profile and blood sugar level estimation can be used as a hallmark tool in evaluation of oral cancer and precancer along with other parameters of biochemical markers. Hence, the reduced serum cholesterol, TGs, and HDL cholesterol, cholesterol in patients with precancerous group and oral cancerous patients which was highly significant in our study may be due to the significant changes in the cell integrity. The present study had some limitations because of small sample size. As a famous saying “Early detection is otherwise called secondary prevention,” thus further research with larger sample size is necessary to record epidemiological data and long follow-up in precancerous and oral cancer patients to determine the mechanisms involved in the lipid profile and blood sugar level initial changes and their independency that take place during carcinogenesis.
The authors would like to acknowledge all patients participated and the Department of Oral Pathology for being helpful in histopathological diagnosis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mishra A, Verma M. Cancer biomarkers: are we ready for the prime time? Cancers (Basel) 2010;2:190-208.
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.
] [Full text]
Ealla RKK, Manikya S, Velidandla S, Prasanna MD, Erugula SR, Kumar A, et al
. Estimation of serum lipid profile in gutkha chewers and oral sub mucous fibrosis patients – A comparative study. Ann Med Health Sci Res 2017;7:5:346-49.
Lohe VK, Degwekar SS, Bhowate RR, Kadu RP, Dangore SB. Evaluation of correlation of serum lipid profile in patients with oral cancer and precancer and its association with tobacco abuse. J Oral Pathol Med 2010;39:141-8.
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.
] [Full text]
Raval GN, Patel DD, Parekh LJ, Patel JB, Shah MH, Patel PS. Evaluation of serum sialic acid, sialyltransferase and sialoproteins in oral cavity cancer. Oral Dis 2003;9:119-28.
Govila V, Govila S, Gupta S, Singh D. Periodontitis: An emerging risk factor for diabetes. Internat Journ of Oral Heal 2015;1:182.
Mehta R, Gurudath S, Dayansoor S, Pai A, Ganapathy KS. Serum lipid profile in patients with oral cancer and oral precancerous conditions. Dent Res J (Isfahan) 2014;11:345-50.
Mujoo S, Shashikant MC, Dubey A, Dubey A. Correlation of lipid profile and glycemia in oral precancerous lesion and conditions. Int J Therap Applic 2016; 33: 119-28.
Gurudath S, Ganapathy K, D S, Pai A, Ballal S, Ml A. Estimation of superoxide dismutase and glutathione peroxidase in oral submucous fibrosis, oral leukoplakia and oral cancer--a comparative study. Asian Pac J Cancer Prev 2012;13:4409-12.
Jahanshahi G, Sabaghian M. Comparative immunohistochemical analysis of angiogenesis and mast cell density in oral normal mucosa and squamous cell carcinoma. Dent Res J (Isfahan) 2012;9:8-12.
Eichholzer M, Stähelin HB, Gutzwiller F, Lüdin E, Bernasconi F. Association of low plasma cholesterol with mortality for cancer at various sites in men: 17-y follow-up of the prospective Basel study. Am J Clin Nutr 2000;71:569-74.
Dikshit RP, Ramadas K, Hashibe M, Thomas G, Somanathan T, Sankaranarayanan R. Association between diabetes mellitus and pre-malignant oral diseases: a cross sectional study in Kerala, India. Int J Cancer 2006;118:453-7.
Neerupakam M, Alaparthi RK, Sathish S, Katta SA, Polisetty N, Damera S. Alterations in plasma lipid profile patterns in oral cancer. J Indian Acad Oral Med Radiol 2014;26:274-8. [Full text]
Prabhu SR, Wilson DF, Daftary DK, Johnson NW. Text Book of Oral Diseases in Tropics. USA: Oxford Medical Publications; 1992. p. 429-46.
Reddi SP, Shafer AT. Oral premalignant lesions: management considerations. Oral Maxillofac Surg Clin North Am 2006;18:425-33.
Gupta PC, Mehta FS, Daftary DK, Pindborg JJ, Bhonsle RB, Jalnawalla PN, et al
. Incidence rates of oral cancer and natural history of oral precancerous lesions in a 10-year follow-up study of Indian villagers. Community Dent Oral Epidemiol 1980;8:283-333.
Proia NK, Paszkiewicz GM, Nasca MA, Franke GE, Pauly JL. Smoking and smokeless tobacco-associated human buccal cell mutations and their association with oral cancer – A review. Cancer Epidemiol Biomarkers Prev 2006;15:1061-77.
Subbulakshmi AC, Mohan N, Thiruneervannan R, Naveen S. Comparative evaluation of serum lipid profile in patients with oral submucous fibrosis and oral squamous cell carcinoma with that of control subjects: A case control study. J Pharm Bioallied Sci 2017;9:S191-6.
Singh S, Ramesh V, Premalatha B, Prashad KV, Ramadoss K. Alterations in serum lipid profile patterns in oral cancer. J Nat Sci Biol Med 2013;4:374-8.
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.
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 Cancer Res Ther 2012;8:384-8.
Chalkoo AH, Singh Risam S, Farooq R. A study on alterations in plasma lipid profile patterns in OSMF patients. J Indian Acad Oral Med Radiol 2011;23:36-8. [Full text]
Janbaz K, Qadir M, Younas F, Malik S. Future strategies in treatment of Parkinson's disease. JCMS-Nepal 2012;23;7.
Anand K, Sudheer A, Chatterjee K. Alteration in serum lipid profile pattern in oral cancer and oral submucous fibrosis patients. J Indian Acad Oral Med Radiol 2018;30:38-40. [Full text]
Meisel P, Dau M, Sümnig W, Holtfreter B, Houshmand M, Nauck M, et al
. Association between glycemia, serum lipoproteins, and the risk of oral leukoplakia: the population-based Study of Health in Pomerania (SHIP). Diabetes Care 2010;33:1230-2.
Alexopoulos CG, Blatsios B, Avgerinos A. Serum lipids and lipoprotein disorders in cancer patients. Cancer 1987;60:3065-70.
Halton JM, Nazir DJ, McQueen MJ, Barr RD. Blood lipid profiles in children with acute lymphoblastic leukemia. Cancer 1998;83:379-84.
Neufeld EJ, Mietus-Snyder M, Beiser AS, Baker AL, Newburger JW. Passive cigarette smoking and reduced HDL cholesterol levels in children with high-risk lipid profiles. Circulation 1997;96:1403-7.
Granero Fernandez M, Lopez-Jornet P. Association between smoking, glycaemia, blood lipoproteins and risk of oral leukoplakia. Aust Dent J 2017;62:47-51.
Gupta SA. Alterations in serum lipid profile patterns in oral cancer and oral precancerous lesions and condition. A clinical study. Indian J Dent. 2011;2:1-7.
Saini R, Al-Maweri SA, Saini D, Ismail NM, Ismail AR. Oral mucosal lesions in non oral habit diabetic patients and association of diabetes mellitus with oral precancerous lesions. Diabetes Res Clin Pract 2010;89:320-6.
Albrecht M, Bánóczy J, Dinya E, Tamás G Jr. Occurrence of oral leukoplakia and lichen planus in diabetes mellitus. J Oral Pathol Med 1992;21:364-6.
Dietrich T, Reichart PA, Scheifele C. Clinical risk factors of oral leukoplakia in a representative sample of the US population. Oral Oncol 2004;40:158-63.
Gong Y, Wei B, Yu L, Pan W. Type 2 diabetes mellitus and risk of oral cancer and precancerous lesions: a meta-analysis of observational studies. Oral Oncol 2015;51:332-40.
[Table 1], [Table 2], [Table 3]