Examination of preoperative and postoperative levels of rare earth elements ( Zn , Cu , Mg , Pb , Mn , Cd , Co and Fe in the blood of ovarian cancer patients

Received 06-01-2015 Accepted 08-06-2015 Available Online 10-01-2015 Yuzuncu Yil University, Faculty of Science, Division of Biochemistry, Department of Chemistry, 65080, Van, Turkey. Yuzuncu Yil University, Faculty of Medicine, Department of Obstetrics and Gynecology, 65080 Van, Turkey. *Corresponding Author: Mustafa Bilici E-mail: mbilici65@hotmail.com Examination of preoperative and postoperative levels of rare earth elements (Zn, Cu, Mg, Pb, Mn, Cd, Co and Fe in the blood of ovarian cancer patients


Introduction
According to World Health Organization (WHO), there are three reasons behind such an increase in cancer cases as follows: smoking, increasing elderly population and obesity.Considering the data obtained from their studies, WHO put forwards that cancer cases will be the first and the most important reason of death across the world after the year 2015 [1,2] According to the data of Ministry of Health, approximately 175,000 people are diagnosed with cancer every year in Turkey.There isn't a statistically significant difference among regions in terms of cancer incidence.The number of deaths arising from cancer is increasingly growing in Turkey.For the last decade, the death rate has increased by 80%.Basing on the research conducted by the Turkish Statistical Institute [3,4,5,6], the rate of cancerrelated deaths reached to 21% in 2012 whereas that rate was 12% in 2002.The incidence of cancerrelated deaths and cancer cases in Turkey increases by the rates similar and parallel to those seen across the world.Apart from those reasons, the fact that the previously-unknown cancer cases have been found out and cancer recording has been improved is another reason behind the increase in cancer statistics.Considering the data obtained by World Health Organization [1,2], the cancer incidence in Turkey is lower than those seen in the countries of America and Europe.Ovarian cancer is increasingly posing a hazard for people lately.Ovarian cancer is highly seen among elderly women and most of the studies deal with aetiology of ovarian cancer because the primary goal should be finding out the different reasons of ovarian cancer.
It is essential to take rare-earth elements at certain rates to enable human organism to maintain its normal functions.These elements join the various structural and functional activities of organism and get involved especially in different enzyme systems and hence they play important roles for occurrence of living phenomena and survival [7].It has been discovered by the studies on different types of cancer within literature that the levels of Zn, Mn, Cu, Mg and Fe sometimes increase and decrease [8,9,10,11].There are a considerably limited number of researches regarding rare-earth elements on ovarian cancer.
In this study, the preoperative and postoperative levels of rare-earth elements (Zn, Cu, Mg, Pb, Mn, Cd, Co, Fe) in blood in ovarian cancer patients were examined.In our research, 3 ml blood was drawn from brachial vein of 33 patients, who were diagnosed with ovarian cancer, before operation and after one month following the operation.The drawn blood was centrifuged in venous biochemistry tube at Nüve NF 800 centrifuge at 5000 rpm for ten minutes and its serum was extracted.The serum was kept at -80 0 C until it was treated.When the adequate number of samples was obtained, the rareearth elements in serum (Zn, Cu, Mg, Pb, Mn, Cd, Co and Fe) were determined by the method of Atomic Absorption Spectrophotometry at Spectrometer: M Series V1,23 in Yüzüncü Yıl University Central Research Laboratory.

Analysis Methods
Determining heavy metal, rare-earth elements and trace elements Trace elements, mineral substances and metals (Zn, Cu, Mg, Pb, Mn, Cd, Co and Fe) were determined from serum samples by the method of Atomic Absorption Spectrophotometry.

Statistical Comments
Regarding the focused properties, the descriptive statistics were expressed as average, standard deviation, minimum and maximum value.In terms of these properties, one-way analysis of variance was performed in order to compare the group averages.Following the analysis of variance, Duncan Multiple Comparison -test was used to determine the different groups.For identifying the relation between these variables, Pearson correlation coefficients were calculated separately for each group.Statistical significance level was taken as 5% (p<0.05) in the calculations for which SPSS statistics package program was used.

Results
This study found out a significant difference (p<0.001) between the preoperative and postoperative levels of lead, manganese and iron in ovarian cancer patients.While a significant difference (p>0.005)wasn't discovered between the preoperative and postoperative levels of zinc, copper, cadmium and cobalt in ovarian cancer patients, a statistically significant difference was found between the preoperative and postoperative levels of magnesium (p=0.07) in those patients.

Discussion
Ovarian cancer ranks the fourth among the cancer-related deaths after breast, lung and colon cancer [12].Ovarian cancer leads to more deaths than the total number of all gynaecological malignance in the United States.204,000 women are diagnosed with ovarian cancer and 125,000 of these women die because of it across the world every year (WHO).Except several particular early symptoms, there isn't an efficient screening test for ovarian cancer.Consequently, ¾ of the patients are at advanced stage of cancer when they are diagnosed.In a research conducted on the patients undergoing chemotherapy in Finland, it was discovered that the patients taking selenium and vitamin E supplement respond to treatment better [13].A study which compared the serum Cu/Zn levels in healthy and gynaecological tumour cases found out that the serum Cu/Zn levels help following up the course of disease [14].There are several studies which put forwards that there is a relation between trace element level and progress of hepatocellular carcinoma.In those studies, the levels of serum, copper, iron and zinc were been found low in liver cancer patients [15].
A research conducted in China revealed that the activity of superoxide dismutase enzyme was low in the patients with hepatocellular carcinoma.The fact that Zn and Cu levels were found low in the same patient group was associated to low enzyme activity.In a study on colon cancer in the literature, Zn level was found higher compared to those of healthy people [10].A research discovered that Zn level in lung cancer patients was significantly lower than those of healthy control group [8].Likewise, a study revealed that Zn level in prostate cancer patients was significantly lower than those of healthy control group [11].This study found out that Zn level in ovarian cancer patients was found higher in preoperative group compared to those of control and postoperative group; but there was no statistically significance (p=0.160).In a study, Cu level in colon cancer patients was found significantly higher compared to those of healthy control group [10].A research on lung cancer discovered that Cu level was lower than those of healthy people [8].This study revealed that Cu level in ovarian cancer patients was lower in preoperative group compared to control group and higher than those of postoperative group; but there was no statistically significance.
A research on colon cancer discovered that Mg level was higher than those of healthy people [10].Mg level in lung cancer patients was found significantly lower than those of healthy control group in a study [8].This study found out that Mg level in ovarian cancer patients was higher in the preoperative group than those of control and postoperative group and was statistically significant.
It was revealed by a study that Pb level in lung cancer patients was significantly higher than those of healthy control group [8].Likewise, a research discovered that Pb level in kidney cancer patients was higher than those of healthy people [9].It was presented by a study in Turkey that Pb level in renal cell carcinoma increased significantly compared to healthy people [16].A literature on colon cancer found out that Pb level was higher than those of healthy people [10].In this study, Pb level in ovarian cancer patients was found higher in the preoperative group compared to control group but lower than those of postoperative group and statistically significant.
Mn level was found higher than those of healthy people in a research regarding colon cancer [10].A study discovered that Mn level in lung cancer patients was significantly higher than those of healthy control group [8].Likewise, it was revealed by a research that Mn level in prostate cancer patients was significantly higher than those of healthy control group [11].This study revealed that Mn level in ovarian cancer patients was lower in the preoperative group than those of control and postoperative group and statistically significant.
A study found out that Cd level in lung cancer patients was significantly higher compared to those of healthy control group [8].It was discovered by a literature on kidney cancer patients that Cd level was higher than those of healthy people [9].A study on colon cancer revealed that Cd level was higher than those of healthy people [10] It was presented by a study in Turkey that Cd level in renal cell carcinoma increased significantly compared to healthy people [16].A study compared Cd levels of glioma cancer patients and healthy people and presented that CD level in glioma patients was significantly higher [17].This study found out that Cd level in ovarian cancer patients was higher in the preoperative group compared to those of control and postoperative group and a result close to statistically significance was obtained.
Co level in lung cancer patients was found significantly higher than those of healthy control group in a research [8].In this study, it was discovered that Co level in ovarian cancer patients was lower in the preoperative group compared to those of control and postoperative group and there was no statistically significance.
A study revealed that Fe level in lung cancer patients was significantly higher than those of healthy control group [8].In a research, Fe level decreased in prostate cancers [11].This study presented that Fe level in ovarian cancer patients was found lower in preoperative group compared to those of control and postoperative group and there was statistically significant difference. This

Conclusion
In conclusion, Zn is important in the prognosis of the disease because it is a strong antioxidant element.Zn level was found high in some studies in literature while it was low in some of them.In our study, Zn level in ovarian cancer patients was found higher in preoperative group compared to control and postoperative group; but a statistically significance wasn't obtained.However, it can be stated that this result is compatible with the literature studies [8,10,11].Likewise, the variations in the levels of Mg, Mn and Fe can be important markers for diagnosis and follow-up of ovarian cancer.Low serum Mn level can be related to ovarian cancer risk.According to these conclusions, such elements as Zn, Cu, Mg, Pb, Mn, Cd, Co and Fe can play an important role in pathogenesis of ovarian cancer.Due to low number of patients and local service of the hospital in our study, we consider it beneficial to conduct studies on wider areas and more patients.We are of the opinion that this study will provide an insight for the further studies to be performed in this field.

Table 1 .
The findings regarding ovarian cancer patients, postoperative and healthy control group

Table 2 .
Correlation coefficients for control group There is positive correlation with Zn and Cu.Cd level: There is a positive correlation with Mg and Pb.Co level: There is positive correlation with Pb and Cd.

Table 3 .
Preoperative correlation coefficients for patient group There is positive correlation with Cu and Mg.Cd level: There is positive correlation with Pb.Co level: There is positive correlation with Mg, Mn and Cd.Fe level: There is positive correlation with Mn.

Table 4 .
Correlation coefficients for postoperative group There is positive correlation with Zn and Cu.Pb level: There is positive correlation with Mg.Mn level: There is positive correlation with Pb and Mg.Cd level: There is positive correlation with Pb, Mg and Mn.Co level: There is positive correlation with Mg, Pb, Mn and Cd.Fe level: There is positive correlation with Zn and negative correlation with Pb, Cd and Co.
study discovered that Mg level in control group had a positive correlation with Zn and Cu values while Cd level had a positive correlation with Mg and Pb.Also it was revealed that Co level had positive correlation with Pb and Cd.In preoperative group, Mg level was found to have positive correlation with Zn.A positive correlation was seen between Mn level and Cu and Mg.Also Cd level had a positive correlation with Pb.While Co level had positive correlation with Mg, Mn and Cd, Fe level had positive correlation with Mn.In postoperative group, Mg level had positive correlation with Zn and Cu.Pb level had positive correlation with Mg; Mn level with Pb and Mg; Cd level with Mg, Pb and Mn; Co level with Mg, Pb, Mn and Cd and Fe level with Zn.Fe level had negative correlation with Pb, Cd and Co.