Elsevier

Clinical Biochemistry

Volume 40, Issue 15, October 2007, Pages 1129-1134
Clinical Biochemistry

Oxidized LDL, serum oxidizability and serum lipid levels in patients with breast or ovarian cancer

https://doi.org/10.1016/j.clinbiochem.2007.06.007Get rights and content

Abstract

Objectives:

The aim of this study was to evaluate the extent of oxidative stress in patients with breast or ovarian cancer by analyzing the magnitude of serum oxidizability and the involvement of oxidized low-density lipoproteins (oxLDL) in the disease.

Design and methods:

The study was conducted on 32 patients diagnosed with breast or ovarian cancer but who had not undergone any kind of treatment and 30 healthy individuals of similar age. The evaluation of oxidative stress was assessed by: (a) the ex-vivo susceptibility of serum lipids to oxidation and (b) the detection of oxLDL and anti-oxLDL autoantibodies. Total cholesterol, LDL-cholesterol and HDL-cholesterol were co-estimated.

Results:

The results indicated that the levels of oxLDL were increased among both breast and ovarian cancer patients as compared to the control subjects. Additionally in patients with breast cancer, serum total cholesterol, LDL-cholesterol, anti-oxLDL antibodies and the maximal rate of diene formation (RA), the index of oxidizable components load, were increased in comparison to controls. There is statistically significant evidence that serum oxLDL levels are associated with increased risk of breast and ovarian cancer.

Conclusions:

The findings exhibit a correlation between oxLDL and malignancy, supporting the contribution of oxidative stress to carcinogenesis and the possible involvement of oxLDL in the process of malignancy. The clinical evaluation of the oxLDL measurement is under investigation.

Introduction

Oxidative stress is a term used to denote the imbalance between the concentrations of reactive oxygen (ROS) and nitrogen (RNS) species and the antioxidative defense mechanisms of the body [1]. Such an imbalance is involved in many clinical conditions, among which are cancer and atherosclerosis [2], [3], [4], [5].

Attack of ROS on biomembranes or on lipoproteins can lead to oxidative destruction of polyunsaturated fatty acids (PUFAs) by a process called “lipid peroxidation”. Lipid peroxidation, the significant characteristic feature of the radical mediated cellular damage both in vivo and in vitro, causes alteration of cell membrane fluidity, decrease in membrane potential and generation of mutagenic lipid epoxides, hydroperoxides, alkoxyl and peroxyl radicals, and in malignancy, increases the risk of metastasis [5], [6]. Hence, in recent years, there has been a growing interest in the study of oxidative stress by analyzing the levels of lipid peroxidation products in cancer patients. An impairment of the antioxidant defense system has been implicated in many diseases including cancer, and the activity of enzymes that contribute to inactivation of free radical reactions has shown different patterns during neoplastic transformation as well as remarkable variability in tumor tissue and in the blood of cancer patients [6], [7], [8]. The most common parameters for oxidative stress evaluation are the determination of antioxidants in serum, the detection of several lipid peroxidation and protein oxidation products, the sensitivity of lipoproteins to oxidation, the determination of oxidized low-density lipoprotein cholesterol (oxLDL) serum levels as well as the concentration of autoantibodies against oxidized biomolecules [1], [9], [10]. Serum or plasma oxidizability is also a practical index of the oxidizability of plasma lipoproteins taking into account the effect of hydrophilic antioxidants on lipid oxidation [1], [9]. However, data concerning the assessment of the above biochemical markers are very limited in clinical practice.

Lipids, lipoproteins and antioxidative vitamins have been associated with the risk of cancer [11], [12]. Previous studies have indicated the positive correlation of lipids and lipoproteins with the risk of breast cancer [13], [14]. On the contrary, low concentrations of total and high-density lipoprotein cholesterol (HDL) were observed in patients with ovarian cancer [15], [16]. Although no causative relation has been established between hyper- or hypo-cholesterolemia and cancer development, possible mechanisms exist through which lipoproteins could contribute to cancer development. LDL is susceptible to oxidation, resulting in increased lipid peroxidation during oxidative stress [14], [17]. Furthermore, oxLDL express a dose dependent mitogenic effect [18]. HDL, on the other hand, prevents both enzymatic and nonenzymatic generation of ROS, and thus, acts as an anticarcinogen and a powerful antioxidant [19]. The present study was conducted to investigate the involvement of oxLDL in the oxidative status in breast and ovarian cancer and to evaluate their probable clinical significance. Serum lipid levels were also co-estimated.

Section snippets

Materials and methods

The study was performed in a group of 32 not overweight post-menopausal women aged 53–70 years with breast (n = 17) or epithelial ovarian (n = 15) cancer admitted to a general hospital in Athens between October 2004 and November 2005. Breast cancer patients were categorized as stage II (n = 6) and stage III (n = 11) according TNM classification [20]. Patients did not receive any chemotherapy or radiotherapy before blood collection. Thirty-five percent of the patients were ex-smokers. The study included

Results

Table 1 shows the characteristics of all the assessed parameters of the studied individuals (control and patient groups). Total cholesterol as well as LDL-cholesterol serum levels was elevated in patients with breast cancer compared to controls, p = 0.0014 and p = 0.0010, respectively, while there was no difference in HDL-cholesterol serum levels. Serum levels of total cholesterol, LDL-cholesterol and HDL-cholesterol did not differ between patients with ovarian cancer and controls. Patients with

Discussion

Cancer is one of the most frequent causes of death worldwide with breast cancer as the most common malignancy in women, accounting for 30% of all cancers diagnosed in women each year [23] while ovarian cancer is the fifth most frequent cancer in women [24]. Multiple factors are likely to contribute to the breast or ovarian cancer incident, though all recognized risk factors together account only for a part of the variability of the incident, leaving the majority of risk factors to be

Acknowledgment

This work was partly supported by the Special Research Accounts of University of Athens.

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    1

    This work constitutes a part of Ioannis Delimaris's PhD thesis.

    2

    Both authors have contributed equally to this work.

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