Orginal Article Serum paraoxonase and arylesterase activities in patients with lung cancer in Turkish population

Background: Lung cancer (LC) is the leading cause of cancer death, and cigarette smoking is the most important cause. Oxidative DNA damage may contribute to the cancer risk. The high density lipoprotein (HDL) associated antioxidant paraoxonase (PON1) is an endogenous free radical scavenger in the human body. The aim of this study was to determine serum PON1 and arylesterase (ARE) activities in patients with newly diagnosed LC and to compare the values with those of healthy controls. Methods: The study was designed in a case control study which consist of the LC group (previously untreated) and ageand sex-matched healthy control group. Serum PON1 and ARE activities and lipid parameters were measured in 39 subjects in both groups. Results: Serum PON1 and ARE activities were found to be decreased in patients with LC compared to controls (p=0,001 and p=0,018, respectively). The ratio of PON1/high density lipoprotein (HDL) was significantly decreased in the LC group compared to the control one (p=0,009). Positive correlation between serum HDL level and serum PON1 level in both the control group (r=0,415, p=0,009) and the LC group (r=0,496, p=0,001) were observed. PON1 enzyme activity was calculated as three different phenotypes in both groups. AA phenotype in the LC group was more than the control group as well BB phenotype was high in the control group. In respect to lipid parameters total cholesterol levels were significantly lower (p=0,014) in the LC group whereas the other lipid parameters such as HDL, LDL, and triglyceride levels were not statistically significant among groups. Conclusion: Serum PON1 activity is significantly low in the LC group compared with the healthy controls. In our study, metastasis status and cigarette smoking do not affect serum PON1 activity in the LC patients. Introduction Lung cancer (LC) is among the most common malignancies in the Western World and is the leading cause of cancer deaths in both men and women. It is one of the few tumors with a known carcinogen, namely tobacco, contributing to its etiology. The leading cause of LC was accepted to smoking. Moreover cigarette smoking was noted in 80% to 90% of patients with LC [1, 2]. An elevated oxidative status has been found in many types of cancer cells, and the introduction of chemical and enzymological antioxidants can inhibit tumour cell proliferation [3]. High doses and/or inadequate removal of reactive oxygen species (ROS) result in oxidative stress, which may cause severe metabolic malfunctions and damage to biological molecules including DNA [4]. It is well known that oxidative stress induced by environmental carcinogen exposure may affect cellular functions in various pathological conditions, including cancer [5, 6]. Human serum paraoxonase (PON1) and arylesterase (ARE) are esterase enzymes that have lipophilic antioxidant characteristics. Serum PON1 binds to high density lipoprotein (HDL) and contributes to the elimination of organophosphorus compounds, such as paraoxon, and carcinogenic lipid soluble radicals from lipid peroxidation. PON1 is one of the endogenous free-radical scavenging systems in the human body [7, 8, 9]. Serum PON1 together with ARE have been demonstrated to function as a single enzyme [10]. PON1 activity varies widely among individuals, partly related to polymorphisms. The PON1 gene has two common coding region polymorphisms [11]. A genetic polymorphism of PON1 activity which determines high versus low paraoxon hydrolysis in human populations [12]. PON1 also has ARE activity, which does not exhibit activity polymorphism and can therefore serve as an estimate of enzyme protein [13]. Human serum PON1 shows neither age-related changes in activity nor sex-dependent activity differences [14]. However, diet, cigarette smoking, acute phase proteins, and pregnancy affect serum PON1 levels and activities [15, 16, 17]. Reduced PON1 activities have been reported in several groups of patients with diabetes mellitus, hypercholesterolemia and cardiovascular disease who are under increased oxidative stress [18, 19]. There are relatively few studies on in PON1 activity in cancer. Serum levels of PON1 were lower in patients with pancreatic or gastric cancer than in healthy controls in two case-control studies. On the other hand, the interaction of serum PON1 levels with cancer is not completely known [15, 20, 21]. It has been emphasized that PON1 polymorphisms might contribute to the increased risk of cancer in associated with pollutants and other environmental chemicals [22]. The aim of our study was to investigate the activity of serum PON1 in patients with LC, compared to that of healthy controls, and to investigate possible alterations related to malignancy. 2. Materials and methods 2.1 The study population This case-control study was conducted at the Department of Internal Medicine of the Fırat (Euphrates) University Hospital setting in Elazig, Turkey, between December 2004 and June 2005. This study was planned for 44 patients. However two of them were excluded from the study due to history of taking antilipidemic drug, three of them were also not eligible for the study due to history of taking chemotherapy. The remaining 39 patients with previously untreated, histopathologically verified newly diagnosed as of LC and 39 ageand sex-matched healthy volunteers were enrolled into this study. Informed consents were obtained from patients prior to the study. The study protocol and the procedures were approved by Firat University Local Ethical Committee, and all subjects were recruited upon obtaining informed consent. Subjects history and physical examinations were documented. The diagnosis of LC was based on histopathologic findings. Nine out of 39 patients were small cell LC, 16 were squamous cell LC, 14 were adenocarcinoma type. Cases either study group or control, who had pathologies that could cause secondary lipid disorders, cardiovascular diseases, diabetes mellitus, renal failure, chronic infection and inflammation, alcohol abuse, and those who used antilipidemic and antioxidant drugs were excluded from the study. Additionally, LC patients with previously performed chemotherapy, radiotherapy and surgery were excluded from the study.