Dyslipidaemia in Cancer
Aparna Dave, Parul Jhamb, Manpreet Kalra
Lipids are essential components of cell membrane and play a vital role in various biological functions including maintaining the integrity of cell. Studies have revealed alterations of lipid profile to be associated with cancer. Not many studies have been carried out to evaluate association of serum lipid levels, oral cancer and precancer. Lower levels of lipids may be due to increased utilisation of lipids by the tumour cells for synthesis of cell membrane. Low levels may also serve as a marker or prognostic indicator of underlying malignancy.
Key Words: Hypolipidemic Agents;Membrane Lipids;Carcinogenesis;Oral Cancer;Precancerous Conditions;Malondialdehyde;Serum Cholesterol.
Aparna Dave, Parul Jhamb, Manpreet Kalra. Idiopathic Dyslipidaemia in cancer. International Journal of Oral & Maxillofacial Pathology; 2011:2(4):83-85. ©International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved.
Received on: 01/10/2011 Accepted on: 01/12/2011
Biochemical evaluations have shown that various substances alter quantitatively during carcinogenesis. Evaluations of biochemical changes like lipid levels1, malondialdehyde levels2 and others may serve as a valuable indicator to predict an early neoplastic change taking place. Lower blood lipids have been associated with various cancers. Some investigators have found relation of low serum cholesterol with increased risk of cancer and mortality.1
Lipids are major cell membrane components and are essential for all animal life. It is primarily synthesized from simpler substances within the body. They play an important role during cell growth & division and in activities of enzymes. They play key role in many vital physiological functions including stabilization of DNA helix.1 It is present in tissues and in plasma lipoprotein either as free cholesterol or combined with a long-chain fatty acid, as cholesterol ester. It is synthesized in many tissues from acetyl-CoA and is ultimately eliminated from the body in the bile as cholesterol or bile salts. However, high levels in blood circulation are strongly associated with progression of atherosclerosis and lipid profile is altered in carcinogenesis.
Since cholesterol is insoluble in blood, it is transported in the circulatory system within lipoproteins . Lipoproteins are clusters of proteins and lipids all tangled together to carry lipids in blood.3There are several types of lipoproteins within blood called chylomicrons , very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Higher densities of lipoproteins are due to more amount of cholesterol as compared to protein moiety. HDL is associated with carrying cholesterol out of the blood system and LDL transports 75% of plasma cholesterol.3 Chylomicrons are lipoprotein transporters in the intestine. VLDL molecules are produced by the liver and contain excess triacylglycerol and cholesterol that is not required by the liver for synthesis of bile acids. LDL molecules are the major carriers of cholesterol in the blood. HDL particles are thought to transport cholesterol back to the liver for excretion or to other tissues that use cholesterol to synthesize hormones. Thus higher levels of HDL are essential for maintenance of healthy tissue.
The different lipoproteins contain apolipoproteins , which serve as ligands for specific receptors on cell membranes. Cellular uptake and regulation of cholesterol is mediated by these receptors located on the cell surface.1 In plasma, triglycerides and cholesterol are packaged into lipoproteins. These lipoproteins are then taken up and degraded by the cells which are needed for functioning of cells. It is believed that levels of lipids vary with malignancy. Lipids are being utilised in maintaining the integrity of cells in the malignant tissue.
Raised levels of lipids have strongly been associated with pathogenesis of coronary heart disease. Hypolipidemia often goes unnoticed and often physicians are unaware of the causes and consequences of
hypolipidemia.4 Lower levels of lipids have been reported to be associated with septicaemia, in critically ill patients4 and at times with the existing malignancy. It may not play a role in carcinogenesis but a lower level of lipids may indicate rapidly dividing cells in malignancy. This can serve as a marker in early neoplastic changes, in follow up cases and as a prognostic indicator of disease. The mechanism for the association of cancer with cholesterol remains controversial. The exact mechanism of its role in carcinogenesis is not clearly defined. Cell membrane is essential for cell survival as well as biological functions.4 Carcinogens induce formation of free radicals which is responsible for high rate of oxidation of polyunsaturated fatty acids. This further releases free radicals which affects the cell membrane. More lipids are required for synthesis of cell membrane1 and the demand is met from degradation of lipoproteins in circulation. It has been suggested that lipid peroxidation product malondialdehyde may cross-link DNA on the same and opposite strands via adenine and cytosine. This may in theory contribute to carcinogenicity.5 Few studies have reported that hypolipidemia may also be attributed to lipid lowering effect of tumour cells or to some secondary malfunction of lipid metabolism or secondary to antioxidant vitamins.6 Genes and hormones also interact to regulate the plasma cholesterol levels.
Mehrotra et al7 carried out a study to evaluate levels of lipid in patients with oral submucous fibrosis and found significant decrease in plasma total cholesterol, HDLC, Apo-A1 levels and believed it to be a useful indicator reflecting initial changes in precancerous and neoplastic conditions7. In another study Gupta et al8 noted that serum cholesterol, HDL and triglyceride levels in case of oral leukoplakia group were significantly less when compared with the healthy control group. But serum cholesterol in case of oral leukoplakia was significantly higher when compared with oral squamous cell carcinoma patients. Serum HDL and serum triglyceride levels were decreased when compared with oral squamous cell carcinoma patients. Serum HDL and serum triglyceride levels were decreased in oral lichen planus group and in oral submucous fibrosis group when compared with both healthy control group and oral squamous cell carcinoma patients8.
A comparative study carried out by Patel et al. to evaluate levels of plasma lipids in head and neck cancer patients, in patients with precancerous condition and in healthy individuals. They found a significant decrease in plasma total cholesterol and HDL levels in cancer patients as well as in patients with precancerous condition as compared to the control group.1 Chawda et al have also found an inverse relationship in lipid levels and occurrence of cancer and found it to be a useful indicator.3 In another study by Lohe et al levels of cholesterol were evaluated in patients with precancer and cancer.6 An significant decrease in Total Cholesterol (TC), HDL, VLDL and triglycerides was noted in patients with cancer. A significant decrease was noted in TC and HDL in patients with oral precancer when compared to control leading to a conclusion of inverse relationship between serum lipid profile and oral cancer and oral precancer.6
Studies have been carried out to evaluate serum lipids levels in patients with other malignancies. Raste et al. evaluated lipid profile in patients with carcinoma of breast, cervix, oesophagus, colon, stomach and leukaemia and concluded that serum total lipids, cholesterol & HDL cholesterol levels were significantly inversely associated with incidence of cancer, whereas triglyceride levels significantly elevated in cancer patients.9 Plasma total cholesterol, LDLC, triglycerides were elevated in breast cancer patients. Schatzkin et al. have noted an inverse association between cholesterol and all cancer.10 Decreased levels of triglycerides & HDL were observed in most of the gynaecologic cancer.5
In recent years emphasis has been given to an early diagnosis of cancer. Various modalities have been applied. Few studies have been carried out to correlate hypolipidemia and oral cancer. An unexplained hypolipidemia should always be investigated for a possible underlying cause. Blood based tests are preferred to evaluate markers in patients with malignancy. These tests are non-invasive, easy to carry out and at times repeated sampling is not cumbersome. Lipid profile can be added on to other tests as an additional indicator and can serve as another evaluating parameter to denote initial changes occurring during carcinogenesis.
1.Dr.Aparna Dave, Professor, 2.Dr.Parul Jhamb, Senior Lecturer, 3.Dr.Manpreet Kalra, Reader, Department of Oral and Maxillofacial Pathology, SGT Dental College and Hospital, Gurgaon, India.
We would like thank all the staff members of the Department of Oral and Maxillofacial Pathology for their support.
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Dr. Aparna Dave,
T-2, 604, Sushant Estate,
Near Ardee City, sector 52,
Gurgaon, Haryana, India.
Source of Support: Nil, Conflict of Interest: None Declared.
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