Microsoft Word - 11 Chemistry | 254 2016) عام 2العدد ( 29الهيثم للعلوم الصرفة و التطبيقية المجلد مجلة إبن Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 Determination of Some Trace Element Levels in Iraqi Male patients with Colorectal Cancer Rana K. Mohammed Salah M. Fezea Dept. of Chemistry, College of Education for Pure Sciences (Ibn Al- Haitham) /University of Baghdad Received in:14/December/2015,Accepted in:7/January/2016 Abstract Alterations of trace element concentrations adversely affect biological processes and could promote carcinogenesis. Trace element deficiency or excess is implicated in the development or progression of some cancers like colorectal cancer. The aim of the present study was to compare the serum copper (Cu) and zinc (Zn) concentrations in patients with colorectal cancer from Iraqi male patient with those of healthy subjects. During the period of March 2015 until august 2015, a total of 25 patients with metastatic colon cancer and 20 healthy volunteers were enrolled from the Al-Kadhimia Teaching Hospital after the diagnosis using a histopathological examination for the malignant tumor; their age was between (38-60) years. Higher levels of Cu, Zn, and Cu /Zn ratio were seen in male patients with colorectal cancer compared to healthy subject's .In Conclusions: According to our findings there was a significant difference in trace elements between healthy subjects and colorectal cancer patients. Key word: Colorectal cancer, Trace elements, Cu/Zn ratio. Chemistry | 255 2016) عام 2العدد ( 29لمجلد ا الهيثم للعلوم الصرفة و التطبيقية مجلة إبن Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 Introduction Colorectal cancer (CRC) is the third most common cancer worldwide with an estimated one million new cases and a half million deaths each year [1]. It is thought to result from complex interaction between inherited susceptibility and environmental factors, as indicated by genetics and experimental and epidemiological studies [2]. Obesity has consistently been linked with an increased risk of colorectal cancer [3]. Numerous epidemiological studies and meta-analyses have examined the relationship between body weight and CRC, mainly risk of colon cancer, and most studies have shown a positive relationship between a high BMI and risk of colorectal cancer [4, 5]. Trace elements have an important influence as a component of many enzymes on a large number of biological processes. They have some regulatory functions and they may affect immune reactions and free radical generation. The extremely low contents of these trace elements and their diversity imply that their molecular effect is very specific and that they may not be substituted for one another. The cancerous tissue directly indicates changes of trace elements that are evoked by the disease. Blood or blood constituents such as serum are considered to be the best indicators of the present exposure of an individual to many metals due to its easy sampling [6]. Therefore, imbalances in the optimum levels of trace elements may affect biological processes and have been associated with many diseases including heart autoimmune, cancer, renal failure and neurological disorders [7]. Copper (Cu) and zinc (Zn), along with other heavy metals, are involved in metabolic processes which regulate energy production. However, despite the fact that they are essential, their high levels cause a toxic effect which can ultimately lead to carcinogenesis [8]. In recent years, the analysis of trace-heavy elements in human tissues has gained great interest due to the role that these elements play in biochemical and physiological processes. It is important to note trace-heavy elements also play an important role in human health and disease. These elements are necessary in different metabolic path- ways of cells and tissues. Each of the essential and non- essential trace elements may be toxic if found in large concentrations in cells, tissues and fluids. Trace element deficiency or excess is implicated in the development or progression in some cancers [9]. The aim of our study was to compare the serum level of copper (Cu), zinc (Zn) and Cu/Zn ratio in patients with colorectal cancer and healthy group and to examine the body mass index factor (BMI) in colorectal cancer. Materials and Methods During the period of March 2015 until august 2015, a total of 25 patients with metastatic colon cancer and 20 healthy volunteers were enrolled. From the Al-Kadhimia Teaching Hospital after the diagnosis using a histopathological examination for the malignant tumor, their age was between (38-60) years. Venous blood samples of patients with metastatic colon cancer, and serum were separated and stored at -2 ºC until analysis. Body mass index measurement Body mass index categories were based on World Health Organization cut points for underweight (18.5 kg/m2), normal weight (18.5 to 24.9 kg/m2), overweight (25.0 to 29.9 kg/m2), and obese (30 kg/m2) [10]. Chemistry | 256 2016) عام 2العدد ( 29لمجلد ا الهيثم للعلوم الصرفة و التطبيقية مجلة إبن Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 Determination of Serum Trace Elements: Determination of serum concentrations of Cu and Zn was performed by Atomic Absorption Spectrophotometer measurements [11]. Statistical analysis The results were analyzed by Student’s t-test using Statistical Package for the Social Sciences (SPSS) version 19. All data were expressed as mean ± SD. P-Value less than 0.05 was considered significant. Results and Discussion: The mean values for the (BMI) and age for male patients with colorectal cancer and control were presented in Table 1. As shown in Table 1, there was a statistically significant association between BMI factor and an increased risk of CRC. The results from this study indicate that the association between obesity and risk of CRC in male. All anthropometric factors were significantly associated with an increased risk of CRC in general, which corresponds well to previous findings [12], [14]. Body weight or BMI have been the most commonly used anthropometric measurements to examine the associations of obesity and colorectal cancer risk, the majority of which have shown a positive relationship between BMI and risk of CRC in men [15] .The associations between sex hormones and risk of CRC in male is poorly understood, but its studies have supported the hypothesis that lower androgen may increase men’s risk of developing CRC [16]. Lower androgen levels seem to be more frequent in obese male, and treatment with testosterone reduces insulin resistance, suggesting a role of androgens in promoting insulin sensitivity and hereby one possible mechanism in the development of CRC. Thus study is consistent with previous studies which shown stronger positive associations for BMI and colorectal cancer incidence [17, 18]. The present work was designed to determine the level of trace elements (Cu, Zn and Cu/Zn ratio) in colorectal cancer in male patients and compare these with healthy controls, table 2. There is a significant increase in the concentrations of Cu, Zn and Cu/Zn ratio in male patients with colorectal cancer when compared with control group. Changes in trace element levels may have prognostic significance in complex disorders including colon rectal cancer. Copper is a redox-active transition metal that can participate in single electron reaction and catalyse formation of free radicals. Beside these properties, it is also an essential element for formation of hemoglobulin, myelin, collagen, and melanin. Copper has been suggested to play an important role in several disorders and normal immune function [19]. Nayak et al. performed a study in 20 patients affected by prostate and colon cancer; they found that Cu and ceruloplasmin levels were increased significantly in the cancer patients as compared to controls [20]. Zinc is an essential trace element that participates as cofactor in a large number of intermediary metabolism proteins, in hormone secretion pathways and in different mechanisms of immune defence. Zinc is known to be an essential component in DNA-binding Zn fingers proteins, as well as in Cu/Zn superoxidedismutase and in several proteins involved in DNA repair mechanisms. Thus, Zn plays an important role in transcription factors function and, antioxidant defence. Dietary deficiencies in Zn can contribute to single- and double- strand DNA breaks and DNA oxidative modifications that increase the risk for cancer development. It is well known that carcinogenesis is a multistep process in which genetic Chemistry | 257 2016) عام 2العدد ( 29لمجلد ا الهيثم للعلوم الصرفة و التطبيقية مجلة إبن Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 sequence alterations helped by environmental factors, such as oxidative stress and antioxidant status [21]. The results of this study partly confirm the observations of other researchers who found that there was a significant difference in trace elements and heavy metals levels between healthy subjects and metastatic colon cancer patients [22]. In current study, high serums level of Zn and Cu were detected in patients with colon cancer. Thus, Zn and Cu may play different role in different types of cancers. In recent years, the analysis of trace-heavy elements in human tissues has gained great interest due to the role that these elements play in biochemical and physiological processes. It is important to note trace-heavy elements also play an important role in human health and disease. These elements are necessary in different metabolic path- ways of cells and tissues. Each of the essential and non- essential trace elements may be toxic if found in large concentrations in cells, tissues and fluids. Trace element deficiency or excess is implicated in the development or progression in some cancers [23]. Conclusion In conclusion, serum levels of Cu and Zn may have prognostic significance in complex disorders including colon cancer. The present findings suggest that imbalance in Cu and Zn trace element level is associated with CRC and might play an important role in cancer development among male Iraqi patients. Environmental factors have an important role in pathogenesis of cancer. Chemistry | 258 2016) عام 2العدد ( 29لمجلد ا الهيثم للعلوم الصرفة و التطبيقية مجلة إبن Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 References 1. Eheman C, Henley SJ and Ballard-Barbash, R. (2012). Annual report to the nation on the status of cancer , 1975-2008, featuring cancers associated with excess weight and lack of sufficient physicalactivity. Cancer., 1(18):2338-2366. 2.Guttmacher, A. E.; Collins, F. S. & Carmona, R. H. (2004). The family history more important than ever. N. Engl. J. Med., 351; 2333–2336. 3. Ning, Y; Wang, L and Giovannucci, EL. (2010). A quantitative analysis of body mass index and colorectal cancer : Findings from 56 observational studies. Obes Rev., 11(1): 19- 30. 4. Pischon, T; Lahmann, PH; Boeing, H; Friedenreich, C; Norat, T; Tjonneland, A; Halkjaer, J; Overvad, K; Clavel-Chapelon, F; Boutron-Ruault, MC,. ( 2006). 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(2012): Association between body mass index and the colorectal cancer risk in Japan: Pooled analysis of populationbased cohort studies in Japan. Ann Oncol 23, 479- 490. 19. Sayır, S; Kavak, I; Meral, H; Demir, N; Cengiz, and U. Cobanoğlu, et al . (2011). ''Effects of Crush and Axotomy on Oxidative Stress and Some Trace Element Levels in Phrenic Nerve of Rats,'' Brain Research Bulletin, 92 (1): 84-88. 20.Nayak, S. B; . Bhat, V. R; D. Upadhyay and Udupa,S. L. ,(2003). Copper and Ceruloplasmin Status in Serum of Prostate and Colon Cancer Patients,''Indian Journal of Physiology and Pharmacology, 47(1):108-110,. 21. Molina-Lopez J; Florea, D; Herrera-Quintana, L ; Adam, V ; Kizek, R ; Quintero ,B and Planells, E et al. (2015). Biomarkers of Zn status associated to colorectal cancer pathogenesis .Journal of Metallomics and Nanotechnologies, 2: 11—18. 22. Ozgur ,E; Halit, D ; Erkan, D; Ramazan, E ; Tugba, G ;Canan, D ; Edip, G ;Nedim, T and Mehmet, F ., (2013). Plasma Concentrations of Some Trace Element and Heavy Metals in Patients with Metastatic Colon Cancer . Journal of Cancer Therapy, 4: 1085-1090. 23. Cobanoglu, U; Demir, H and Sayir, F., (2010). Some Mineral, Trace Element and Heavy Metal Concentrations in Lung Cancer Asian Pacific Journal of Cancer Prevention, 11( 5) : 1383-1388. Chemistry | 260 2016) عام 2العدد ( 29لمجلد ا الهيثم للعلوم الصرفة و التطبيقية مجلة إبن Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 Table (1) Demographic and anthropometric features of colorectal cancer patients and controls. Characteristics Patients Control P-Value Number 20 20 - Age (Years) 48.95±5.09 48.50±5.18 0.36 NS BMI (Kg/m2) 30.1±0.30 25.39±3.1 0.001 Family history of colorectal cancer 75% --- ---- Table( 2) Trace element levels in colorectal cancer patients and controls NS: not significant Characteristics  Patients   Control           P‐Value  Cu (µg/dl)  152.0 ± 0.12  78.0±0.04  0.001  Zn (µg/dl)  101.0± 0.50  70.0±0.22  0.001  Cu/Zn ratio  1.50±0.24 1.11±0.18  0.05  Chemistry | 261 2016) عام 2العدد ( 29لمجلد ا الهيثم للعلوم الصرفة و التطبيقية مجلة إبن Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 مستويات بعض العناصر النزرة(نحاس ,زنك,نسبة نحاس/زنك )عند مرضى .الرجال العراقيين المصابين بسرطان القولون المستقيم رنا كريم محمد صالح محمد فزع قسم الكيمياء/كلية التربية للعلوم الصرفة(ابن الهيثم)/جامعة بغداد 2016كانون الثاني//7،قبل في:2015كانون األول//14استلم في: الخالصة العناصر النزرة تؤثر سلبا في العمليات البيولوجية ويمكن أن تعزز زيادة او نقص عنصر التغيرات في تراكيز في تطور بعض أنواع السرطان مثل سرطان القولون والمستقيم. ان الهدف من هذه الدراسة هو مقارنة تركيز النحاس و ن والمستقيم مع تلك المجموعة من الزنك في مصول الذكور من المرضى العراقيين الذين يعانون من سرطان القولو ، تم تسجيل مجموعه تتالف من خمسة وعشرين من المرضى الذين يعانون من 2015مارس وأغسطس مابيناألصحاء. الفحص عمال سرطان القولون المنتشر وعشرين متطوعا من األصحاء. من مستشفى الكاظمية التعليمي بعد التشخيص باست ). وقد شوهدت مستويات أعلى من النحاس والزنك 38-60ن متوسط أعمارهم تتراوح بين (المجهري للورم الخبيث،وكا ونسبة النحاس / الزنك في المرضى من الذكور المصابين بسرطان القولون والمستقيم بالمقارنة مع االشخاص االصحاء، صر النزرة الصحية والمرضى بسرطان وكانت هذه النتائج ذات داللة إحصائية اذ وجد فرق كبير او تباين ملحوظ في العنا القولون والمستقيم. : سرطان القولون المستقيم, العناصر النزرة,نسبة النحاس/الزنك. كلمات مفتاحية