Comparative Study of Serum Lipid Profile in Tobacco Addicts, Tobacco Non-addicts and Head–Neck Malignancy

Abstract

The present study was undertaken to evaluate lipid profile in tobacco consumers with and without head and neck malignancy and to see whether tobacco consumption causes same degree of alteration in lipid profile. Prospective study of serum lipid profile in 90 patients was done at Govt. Medical College Hospital. Various details of all participants such as age and sex of patients, detailed history of tobacco consumption were taken. Patients were divided into group I, II and III. Serum lipid profile was studied in 30 patients with tobacco addicts for more than 5 years in the form of tobacco chewing and smoking without head–neck malignancy (Group I), 30 patients with tobacco addicts for more than 5 yrs in the form of tobacco chewing and smoking with head–neck malignancy (Group II) and 30 controls i.e., non-smokers and non-tobacco chewers (Group III). Statistical analysis was done to compare the serum lipid profile (Total Cholesterol, HDL, Ratio, Sr. triglyceride, VLDL, LDL) among the tobacco chewers with head and neck malignancy, non-tobacco consumers and tobacco consumers without malignancy and controls i.e., non-smokers and non-tobacco chewers. There was no significant change in total cholesterol, LDL, VLDL, HDL in patients with tobacco addicts and tobacco non-addicts. Serum triglycerides are significantly decreased in tobacco addicts and in malignancy. Total cholesterol, HDL, and LDL are significantly increased in malignancy as compared to tobacco addicts and tobacco non-addicts. There was no significant change in total cholesterol, LDL, VLDL, HDL in patients with tobacco addicts and tobacco non-addicts. Serum triglycerides are significantly decreased in tobacco addicts and in malignancy.

Introduction

Tobacco consumption is one of the major causes for oral malignancy [1]. Nicotine is the active ingredient in tobacco. Nicotine stimulates sympathetic adrenal system by increasing the secretion of catechol amines, which result in increased lipolysis [2]. Cigarette smoking is known to be associated with raised plasma Homocysteine level [3, 4]. Raised plasma Homocysteine level causes oxidative modification of LDL-Cholesterol and decreases HDL-Cholesterol [5]. Several studies reported that plasma homocysteine levels are raised in tobacco consumers, which inhibit Apo A-I protein expression and leads to decrease in HDL Cholesterol levels [6, 7].

Various carcinogens in tobacco induce generation of free radicals and reactive oxygen species, which in turn are responsible for oxidation/peroxidation of polyunsaturated fatty acids. Lipid peroxidation may play an important role in cancer development as a 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 carcinogenicity, and mutagenicity in mammalian cells [8].

Lipid peroxidation may be induced by tobacco carcinogens that are known to produce reactive oxygen species and lipid peroxides. This lipid peroxidation affects the essential components of cell membranes. Williams et al. [9] suggested that lower level of serum cholesterol levels in cancer patients may be due to increased membrane permeability to carcinogens induced by trans fatty acids [10]. For new membrane biosynthesis there is a greater utilization of lipids like TC, TGL and lipoproteins. Newly forming and rapidly proliferating malignant cells need many basic components such as lipids. Such lipid requirement is fulfilled either from circulation, by synthesis through metabolism or from degradation of major lipoprotein fractions like VLDL, LDL or HDL [1, 10]

Serum cholesterol levels returning to normal in patients who are responding to cancer treatment suggested that tumor burden was inversely related to cholesterol levels rather than the tendency of individuals with lowered cholesterol to develop cancer [11, 12]. Blood cholesterol levels are important parameter in diagnosis and treatment of cancers [13]. There is an association of variations in blood cholesterol levels, plasma lipids and lipoproteins in different cancers and therefore they are important parameters in prognosis, diagnosis and treatment of different cancers. Hypolipidemia at the time of diagnosis is a causative factor for cancer or cancer leads to hypolipidemia is not yet cleared [14].

The present study is aimed to evaluate the plasma lipid profile in tobacco consumer patients with and without head and neck malignancy. The association between alterations in plasma lipid profile in head and neck malignancy is also being studied.

Materials and Methods

The study is a prospective observation carried out at govt. medical college hospital, Solapur (Maharashtra). Total 90 patients were included in the study. Serum lipid profile was studied in 30 patients with tobacco addicts for more than 5 years in the form of tobacco chewing and smoking without head–neck malignancy, 30 patients with tobacco addicts for more than 2 years in the form of tobacco chewing and smoking with head–neck malignancy and 30 controls, i.e., non-smokers and non-tobacco chewers.

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 Tobacco consumption were taken. ENT examination was done for every participant. The inclusion criteria are Tobacco addict patients between age groups 15 and 70 years with malignant head and neck lesion (Group II). Tobacco addiction includes tobacco smoking, tobacco chewing, sniff, Shisha smoking, etc. Tobacco addicts patients between age groups 15 and 70 years (Group I). Control group was included in the study (Group III). Patients without tobacco addiction and without any malignant head and neck lesion whose age and sex matched were taken as control group. Patients with Diabetes mellitus, hormonal disorders, obesity, cardiac disease, renal disease, liver disease and patients below 15 years age were excluded from study.

The Ethical Committee clearance was obtained.

Lipids Analysis

The samples collected from the subjects were centrifuged and the collected plasma was stored at 80 °C until analysed. Serum total cholesterol estimation was done by modified Roeschlau,s method. Serum triglyceride TC levels were estimated using McGowan and Fossat method. Estimation of Serum HDL Cholesterol was done by phosphotungstic method. VLDL-c and LDL-c estimation was done by Friedewald formula.

Very low-density lipoprotein cholesterol (VLDLC) and low-density lipoprotein cholesterol (LDLC) were calculated using the formula given below

$$\text{VLDLC}=\text{TG}/5$$

$$\text{LDLC}=\text{TC}-\text{VLDLC}-\text{LDLC}$$

Statistical analysis was done to compare the serum lipid profile (Total Cholesterol, HDL, Ratio, Sr. triglyceride, VLDL, LDL) among the tobacco chewers with head and neck malignancy, non-tobacco consumers control and tobacco consumers without malignancy and controls i.e., non-smokers and non-tobacco chewers.

Results

Male and Female Distribution in the Study Group (Group II)

In the present study, males were more prone to develop malignant lesions than females. Males addicted to tobacco than females. Also Indian cultural practices such as application of lime to tobacco, Quit which includes pan with tobacco, gutkha and betel nut are more common in males. Tobacco use by males is socially accepted.

Serum Lipid Profile in Tobacco Consumers

In the present study, serum lipid profile was higher side in tobacco consumers (Table 1).

Table 1.

Upper and lower limit of Serum lipid profile in tobacco addicts

Tobacco addict	Total cholesterol	HDL	Ratio	Sr. triglyceride	VLDL	LDL
Mean	169.30	43.17	3.91	86.10	18.90	108.67
SD	19.29	3.39	0.33	26.80	5.63	16.44
Lowerlimit	131.48	36.51	3.26	33.57	7.87	76.45
Upperlimit	207.12	49.82	4.56	138.63	29.93	140.88

There are variations in upper and lower limit of serum lipid profile. The variations are due to the variations in tobacco consumption, duration, and Tobacco consumption pattern, frequency of tobacco consumption and age of the patient. In the young patient duration of tobacco consumption is less. In the present study, serum lipid profile was higher side in tobacco consumers. But there is no significant increase in serum lipid profile in tobacco consumers (Tables 2, 3).

Table 2.

Upper and lower limit of Serum lipid profile in tobacco non-addicts

Tobacco non-addict	Total cholestrol	HDL	Ratio	Sr. triglyceride	VLDL	LDL
Mean	171.93	42.70	4.00	100.53	19.90	103.23
SD	29.01	3.91	0.40	36.60	6.70	33.87
Lowerlimit	115.07	35.05	3.21	28.80	6.76	36.84
Upperlimit	228.80	50.35	4.79	172.27	33.04	169.62

Table 3.

Comparison of Serum lipid profile in tobacco addicts and tobacco non-addicts

	Total cholesterol	HDL	Ratio	Sr. triglyceride	VLDL	LDL
PSD	25.06	3.72	0.37	32.62	6.29	27.08
T test	− 0.41	0.49	− 0.95	− 1.71	− 0.62	0.78
p value	p > 0.05	p > 0.05	p > 0.05	p < 0.05	p > 0.05	p > 0.05
	NS	NS	NS	Significant	NS	NS

There is no significant difference in Total cholesterol, HDL, triglyceride, LDL and VLDL in tobacco addict and tobacco non-addict group. Serum triglycerides are significantly decreased in tobacco addict group

Discussion

Lipids are essential for cell membrane formation, energetic, biophysical and signalling pathways that drive tumorigenesis. Increase or decrease production of specific signalling lipids and disturbed lipid metabolism are indicators of cancer [15, 16]. Tobacco contains nicotine which leads to increasing levels of lipids in the blood [17]. Low serum cholesterol is associated with increased risk of cancer occurrence and mortality [18, 19]. Tobacco addict patients with cancer may have different lipid profile pattern.

Low Density Lipoprotein Cholesterol and Very Low Density Lipoprotein Cholesterol

In present study, LDL cholesterol is significantly increased in malignancy as compared to both tobacco addicts and tobacco non addicts (Tables 4 and 5)

Table 4.

Comparison of Serum lipid profile in tobacco addicts and malignancy

Cancer	Total cholesterol	HDL	Ratio	Sr. triglyceride	VLDL	LDL
Mean	198.60	45.40	4.35	69.73	20.00	135.40
SD	26.10	3.50	0.33	16.89	6.42	19.14
Lowerlimit	147.44	38.54	3.70	36.63	7.42	97.89
Upperlimit	249.76	52.26	5.00	102.84	32.58	172.91
PSD	23.34	3.51	0.34	22.78	6.14	18.14
t test	− 4.86	− 2.47	− 5.07	2.78	− 0.69	− 5.71
p value	p < 0.01	p < 0.01	p < 0.01	p < 0.01	p > 0.05	p < 0.01
	HS	HS	HS	HS	NS	HS

Total cholesterol, HDL and LDL are significantly increased in malignancy. Sr. triglyceride is significantly decreased in malignancy

Table 5.

Comparison of serum lipid profile in tobacco non addicts and malignancy

Cancer	Total cholesterol	HDL	Ratio	Sr. triglyceride	VLDL	LDL
Mean	198.60	45.40	4.35	69.73	20.00	135.40
SD	26.10	3.50	0.33	16.89	6.42	19.14
Lowerlimit	147.44	38.54	3.70	36.63	7.42	97.89
Upperlimit	249.76	52.26	5.00	102.84	32.58	172.91
PSD	28.07	3.77	0.38	28.99	6.67	27.98
t test	− 3.68	− 2.77	− 3.58	4.11	− 0.06	− 4.45
p value	p < 0.01	p < 0.01	p < 0.01	p < 0.01	p > 0.05	p < 0.01
	HS	HS	HS	HS	NS	HS

Total cholesterol, HDL and LDL are significantly increased in malignancy. Serum triglyceride is significantly decreased in malignancy

In studies conducted by Singh et al. and Chawda et al. serum LDLC and VLDLC levels did not reveal any significant difference between the cancer and control groups [12, 20]. According to Benn et al. [21], low LDL cholesterol levels do not associated with cancer occurrence. In the present study, LDL is significantly increased in tobacco addicts with malignancy but there is no significant change in VLDL in malignancy.

Correlation of Lipid Profile with Tobacco Addict

Different forms of tobacco are consumed in the society. Tobacco contains many carcinogens like nicotine and nitrosamines, which are believed to induce new free radicals and reactive oxygen species, which are responsible for the high rate of oxidation/peroxidation of polyunsaturated fatty acids which are the important components of cell membranes. This peroxidation further releases peroxide radicals. These free radicals affect essential constituents of cell membrane resulting in tissue injury. Free Peroxide radicals damage the cellular structural blocks such as lipids. Thus lipids are disturbed in carcinogenesis or tumorigenesis [18, 19].

Total Cholesterol

In the present study, total cholesterol is significantly increased in malignancy (Tables 4 and 5).

As cholesterol is required for cell membrane formation, low levels of cholesterol in the proliferating tissues and in blood compartments could be due to angiogenesis in cancer patients. Studies have reported that hypolipidemia may result due to either the direct lipid lowering effect of tumour cells or some malfunction of the lipid metabolism. Hypolipidemia may be secondary to effect of antioxidant vitamins [10]. Cholesterol is an essential constituent of lipoprotein fractions like HDL-C, LDL-C and VLDL-C. Seventy-five per cent of the plasma cholesterol is transported in the form of LDL-C. Body cells sequester cholesterol from the LDL-C fraction of lipoproteins. LDL receptors are necessary for metabolizing circulating LDLC levels and nearly 80% of the plasma LDLC is cleared by LDL receptors [18, 22]. High activity of LDL receptors leads to lowering the serum cholesterol levels [18]. Studies have shown a highly significant reduction in the levels of TC in the oral cancer group [20].

It has been consistently observed that in some malignant diseases, blood cholesterol undergoes early and significant changes. Several prospective and retrospective studies have shown an inverse association between blood lipid profile and different cancers. Lohe et al. [19] have observed an inverse relationship between serum lipid profile and oral cancer and oral pre-cancer [10]. Patel et al. [18] have also observed an inverse relationship between lower plasma lipid profile and head and neck malignancies and oral precancerous conditions [1, 9]. Naheed Quaid Memon et al. [23] estimated that lowering the serum cholesterol of the whole population by 10% should lengthen median life by 1 year, but the percentage of deaths from cancer should rise from 26.8 to 29.6% [12]. Thus, he explains that there is a 3% more mortality due to hypocholesterolemia in cancer patients. According to Naheed Quaid Memon et al. hypocholesterolemia is a cause of cancer. However, it has not been still proved whether hypocholestremia is a cause or effect of cancer. In the BUPA study, done by Wald [24] proved that low serum cholesterol is not a cause of cancer. Rose et al. reported 66% higher mortality rate in cancer with lowest plasma cholesterol than cancer with the highest plasma cholesterol.

Triglycerides

As far as TGL levels in cancer patients are concerned, there are different opinions. In the present study, there is significant decrease of serum triglyceride levels in malignancy as compared with tobacco non-addicts (Table 5).

Some of the studies reporting significant reduction in TGL levels in cancer patients as compared with the controls [12, 20, 22]. Some have found a non-significant difference in serum TGL between controls and malignancy patients. Furthermore, still others have observed elevated TGL levels in cancer patients [18].

The reduced levels of TGLs observed can be explained on the basis that some decrease will be there when there is increased utilization of lipid particles due to new membrane formed during the process of carcinogenesis and also due to lipid peroxidation of cell membrane because of tobacco carcinogens. Although they are not the major part of the cell membrane as the cholesterol, they constitute a part of the cell membrane up to some extent. So, it is suggested that both of these factors can affect the total plasma triglyceride levels.

High Density Lipoprotein Cholesterol

HDL-C levels may also serve as a useful indicator, in neoplastic conditions [22]. Decrease in the HDLC levels have been observed in numerous reports [12, 20]. It might be a consequence of a disease that is mediated by utilization of cholesterol for membrane biogenesis of the proliferating malignant cells [12, 20].

In the present study, there is significant increase of HDL in malignancy.

Key Message

Lipid profile is deranged in tobacco consumers with and without head and neck malignancy.

Limitations of Study

Stage of malignancy is not taken in account. Further study requires in large study group and in all grades of malignancy.