Evaluation and Correlation of Serum Lipid Profile in Oral and Gastrointestinal Cancer Patients

Abstract

Background: High or low cholesterol levels can be perturbing. High cholesterol levels in the blood are associated with increased risk of coronary heart disease whereas insinuation of decreased cholesterol levels remains imprecise. Present study is to evaluate any relationship between the serum lipid levels and the cancer. The purpose of this study is to evaluate the alteration of serum lipid profiles in untreated mucosal cancer patients. Materials & Methods: The study sample consisted of thirty subjects (Group I – 10 gastrointestinal cancer patients, Group II - 10 oral cancer patients and Group III - 10 controls). Fasting lipid profile of blood was evaluated using spectrophotometric kits, with CHOD PAP technique. The values obtained were then statistically analyzed using ANOVA and student ‘t’ test. Results: Between Group I and II, Group I comparatively showed more decrease in TC, TG, VLDL and increase in HDL & LDL. P value was significant in only TG. Between Group II and III, TC, HDL and LDL were decreased whereas TG and VLDL were increased in Group II when compared to Group III. TG, LDL, VLDL showed significant p values. Between Group I and III, the variables showed similar results as seen between Group II and III but only LDL showed significant p value. Among the three groups, only LDL showed significant p value (0.048). TC, TG, HDL and VLDL showed non – significant p values. Conclusion: Lower levels of lipid should arouse suspicion for cancer and necessary screening should be done. How to cite this article: Srinivas GV, Namala S, Ananthaneni A, Puneeth HK, Devi BS. Evaluation and Correlation of Serum Lipid Profile in Oral and Gastrointestinal Cancer Patients. J Int Oral Health 2013; 5(6):72-7 .

Introduction

Proteins and lipids form specialized clusters in blood called as lipoproteins, which all tangled up together to carry lipids in our blood. These form fundamental component of cell membrane and play a vital role in cell growth and division and are also required for maintaining the cell integrity of normal and malignant tissues. Energy in the body is mainly stored as triglycerides (TGs). TGs and cholesterol are first packed into lipoproteins and transported in plasma and later are taken up and degraded by cells for the cellular functions. Cholesterol, the known etiological factor of coronary heart disease, has recently become the focus of attention on the possible role in the etiology of cancer. Several authors propose that hypocholesterolemia to be a predisposing factor for cancer development. 1 , 2 So the aim of the present study is to assess the relation between the lipid profile levels and cancer. Since both oral and gastrointestinal cancers come under the mucosal cancers, lipid profiles of both the cancers have been compared in the present study along with the normal patients.

Materials and Methods

The study included total of thirty subjects, 10 were histopathologically diagnosed oral cancer patients, 10 gastrointestinal cancer patients and 10 controls with no systemic disease. Two milliliters of fasting blood was collected from each patient in red color-coded vacutainers and the blood was allowed to clot. Serum was then obtained by centrifuging this clotted blood. Chemical analyzer (Erba chem 5x analyzer) based on spectrophotometric principle was used for lipid analysis. Enzymatic photometric test was used for analysis using a wavelength of 546 nm and an optical path of 1 cm and is known as "CHOD PAP". The serum lipid profile was analyzed on the same day of the withdrawal of blood which included TC, TG, HDL, LDL, and VLDL. Analysis of variance (ANOVA) and student 't' style="test statistical analysis were used. A value of p<0.05 was considered significant.

Results

Out of 10 oral cancer cases, 7 (70%) were male patients, 3 (30%) were female patients, 1 (10%) recorded in alveolus, 5 (50%) in buccal mucosa, 1(10%) in hard palate, 3 (30%) in tongue.

In gastro intestinal cancer, out of 10, 3 (30%) were male patients, 7 (70%) were female patients, 2 (20%) in colon, 3 (30%) oesophagus, 5 (50%) stomach. (Table 5 and 6) Gastro intestinal cancer patients were in the age range 28-75 with mean age of 50.40±14.82, oral cancer patients with age range 35-67 with mean age of 54.20±11.74, controls with age range 25-65 with mean age of 48.50±12.87. (Table 7)

Table 5: Sex-distribution of cases

Sex	Gastrointestinal Cancer	Oral Cancer	Normal	Total
Male	3 (30%)	7 (70%)	6 0%)	16
Female	7 (70%)	3 (40%)	4 (40%)	14
Total	10	10	10	30

x2 = 3.482; df = 2; p = 0.175; Not Significant

Table 6: Site-distribution of cases

Cancer	Gastrointestinal Cancer	Oral Cancer
Colon	2	-
Oesophagus	3	-
Stomach	5	-
Alveolus	-	1
Buccal Mucosa	-	5
Hard Palate	-	1
Tongue	-	3
Total	10	10

Table 7: Comparison of age in three Groups

Group	N	Range	Age ears) Mean ± SD	ANOVA
I. Gastrointestinal Cancer	10	28 – 75	50.40 ± 14.82	F = 0.483;
II. Oral Cancer	10	35 – 67	54.20 ± 11.74	p = 0.622
III. Normal	10	25 – 65	48.50 ± 12.87	Not Significant
Total	30	25 – 75	51.03 ± 12.97

Between Group I and II:

When compared to Group II, Group I showed more decrease in TC, TG, VLDL and increase in HDL and LDL but TG only showed significant p value (0.452). (Table 1)

Table 1: Comparison between Group I and II (student ‘t’ test)

	Group I (n = 10)	Group II (n=10)	‘t’ value	P value
TC	160.50 ± 48.98	163.10 ± 32.66	0.140	0.890NS
TG	141.80 ± 66.34	165.10 ± 69.08	0.769	0.452*
HDL	43.00 ± 7.10	42.30 ± 7.50	0.214	0.833NS
LDL	89.50 ± 37.18	87.20 ± 35.83	0.141	0.890NS
VLDL	28.20 ± 13.16	33.60 ± 14.22	0.881	0.390NS

NS: p > 0.05; Not Significant; * p < 0.05; Significant

Between Group II and III:

TC (163.10 ± 32.66), HDL (42.30 ± 7.50) and LDL (87.20 ± 35.83) were decreased whereas TG (165.10 ± 69.08)

and VLDL (33.60 ± 14.22) increased in Group II when compared to Group III (TC 186.60 ± 14.32, HDL 43.80 ± 5.75, LDL 119.40 ± 13.31, TG 114.40 ± 16.14, VLDL 22.40 ± 3.13). TG, LDL, VLDL showed significant p values (0.036, 0.016, and 0.026 respectively). (Table 2)

Table 2: Comparison between Group II and III (student ‘t’ test)

	Group II (n=10)	Group III (n=10)	‘t’ value	P value
TC	163.10 ± 32.66	186.60 ± 14.32	2.084	0.052NS
TG	165.10 ± 69.08	114.40 ± 16.14	2.260	0.036*
HDL	42.30 ± 7.50	43.80 ± 5.75	0.502	0.622NS
LDL	87.20 ± 35.83	119.40 ± 13.31	2.664	0.016*
VLDL	33.60 ± 14.22	22.40 ± 3.13	2.432	0.026*

NS: p > 0.05; Not Significant; * p < 0.05; Significant

Between Group I and III:

The variables showed similar results (TC 160.50 ± 48.98, HDL 43.00 ± 7.10, LDL 89.50 ± 37.18, TG 141.80 ± 66.34, VLDL 28.20 ± 13.16) as seen between Group I and III but only LDL showed significant p value (0.028). (Table 3)

Table 3: Comparison between Group I and III (student ‘t’ test)

	Group I (n = 10)	Group III (n=10)	‘t’ value	P value
TC	160.50 ± 48.98	186.60 ± 14.32	1.617	0.123NS
TG	141.80 ± 66.34	114.40 ± 16.14	1.269	0.221NS
HDL	43.00 ± 7.10	43.80 ± 5.75	0.277	0.785NS
LDL	89.50 ± 37.18	119.40 ± 13.31	2.394	0.028*
VLDL	28.20 ± 13.16	22.40 ± 3.13	1.355	0.192NS

NS: p > 0.05; Not Significant; * p < 0.05; Significant

Among the three Groups:

Only LDL showed significant p values (0.048). TC, TG, HDL and VLDL showed non – significant p values. (Table 4)

Table 4: Comparison among the Groups (ANOVA)

	Sum of Squares	df	Mean Square	F	P value
TC	Between Groups	4134.067	2	2067.033	1.689	0.204NS
	Within Groups	33041.800	27	1223.770
	Total	37175.867	29
TG	Between Groups	12880.467	2	6440.233	2.048	0.149NS
	Within Groups	84906.900	27	3144.700
	Total	97787.367	29
HDL	Between Groups	11.267	2	5.633	.121	0.887NS
	Within Groups	1257.700	27	46.581
	Total	1268.967	29
LDL	Between Groups	6453.800	2	3226.900	3.405	0.048*
	Within Groups	25590.500	27	947.796
	Total	32044.300	29
VLDL	Between Groups	627.467	2	313.733	2.442	0.106NS
	Within Groups	3468.400	27	128.459
	Total	4095.867	29

NS: p > 0.05; Not Significant; * p < 0.05; Significant;

Discussion

Lipids form the essential and vital part of the cell membrane and are required for diverse biological functions such as cell growth and division of normal and malignant tissues, for DNA helix stabilization, maintenance of both structural and functional integrity of all biological membranes and for activity of membrane-bound enzymes. 1 - 3 Cholestrol, being insoluble in blood are transported using lipoproteins. Lipoproteins are the masses of proteins and lipids all entangled together to carry lipids in blood. These include chylomicrons, very-low-density lipoprotein (VLDL), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). HDL clears "cholesterol" out of the blood system back to the liver for excretion or takes it to other tissues for synthesizing hormones. 75% of plasma cholesterol is transported to blood by

LDL. Circulating LDL is metabolized by cell receptors and clears nearly 80% of it from the body, while the remaining of it is associated with deposition of "cholesterol" on the walls of arteries. This is considered to be the pathogenesis of coronary heart disease which is depicted as hyperlipidemia. But hypolipidemia often goes overlooked as the physicians are naive of the causes and consequences of hypolipidemia. 1 , 2

Many studies have found a significant decrease in plasma lipid levels in cancer patients when compared to controls. Controversy still exists regarding the mechanism of association of cancer with cholesterol. The exact role of lipid levels in carcinogenesis is not clear. 1 , 2 The following hypothesis were given by various authors for decrease in the lipid levels in cancer patients.

1. Cholesterol levels may decrease preceding the cancer manifestation or due to the secondary association with cancer.

2. Some forms of cancer demonstrate lower cholesterol values before its development and may be associated with in causally.1,3

3. Diminished lipid stores are due to increased demand of lipids above the normal physiological levels by malignant cells for the purpose of cell growth and division.1,2,4,5

4. Free radicals produced by the carcinogens cause increased rate of oxidation of polyunsaturated fatty acids which further release free radicals affecting the cell membrane. Cancer cells, for the synthesis of cell membrane, obtain lipids by degradation of lipoproteins in circulation.1,2

5. Oral cancer interferes significantly on food intake as well as lipid ingestion and absorption.

6. Increased LDL receptor activity in tumor cell may produce hypocholesterolemia.3

7. May be due to antioxidant vitamin therapy.

8. Malondialdehyde, the lipid peroxidation product may play an important role in the carcinogenesis by cross linking DNA on the same and opposite strand via adenosine and cytosine. Tobacco carcinogens also produce reactive oxygen species and lipid peroxides and thus play a role in carcinogenesis.4

9. Tumor metabolites may inhibit the synthesis of lipoproteins and cholesterol by the liver.6

The above reasons can be used to explain the lower total cholesterol levels in our study in both Group I and II.

The present study showed significant decrease in the plasma LDL and increase in TG levels in Group II when compared to Group III which is in contrast to study done by Chawda et al.,1 Lohe et al.,3 Patel et al., 7 where LDL and TG showed a non – significant decrease. The low levels of LDL-cholesterol might be due to high susceptibility of LDL to oxidation in various pathologic conditions when compared to HDL and also due to increased LDL receptor activity in cancer which increases the TC and LDL uptake by the cells. 3 , 4 , 7 , 8

LDL in the Group I showed statistical decrease when compared to Group III. Other variables did not show any significant p values with decrease in TC and HDL and increase in TG and VLDL. Statistical increase in the TG levels of Group II in the present study was in consistent with study done by Raste et al.6 Lipid mobilising factor (LMF) and tumour (and host) factor zinc-alpha-2 glycoprotein causes an increase in lipolysis in the early stages of cancer cachexia before the manifestation of disease resulting in increased production of TG that is in turn used for the production of VLDL. Later VLDL enters the blood stream. This might be the cause for the increase in both TG and VLDL in the cancer patients in our study. 9

Significant decrease in TC, HDL, VLDL, and TG in oral cancer group; and significant decrease in TC, and HDL in oral precancer group as compared to controls was observed by Lohe et al.3 Chawda et al.1 found a significantly lower levels of total lipids, cholesterol and HDL in oral cancer patients when compared to controls, but LDL and VLDL values were not significant. Kumar P et al.4 observed much lower TC, HDL, and LDL values in the cancer group compared with controls.

When compared to Group II, Group I showed decrease in TC, VLDL and TG with p value significant only in TG. This can be due to the highest frequency of developing cachexia in gastrointestinal cancer patients than in oral cancer patients. 9

Conclusion

Lipid levels except for TG and VLDL showed an inverse relationship with the occurrence of mucosal cancer. Gastrointestinal patients show more decrease due to higher frequency of cachexic symptoms. Lower levels of serum lipid should prudence for every possibility of cancer and necessary screening should be done to diagnose at early stages.