Journal of Cancer Therapy, 2013, 4, 1085-1090
http://dx.doi.org/10.4236/jct.2013 46124 Published Online August 2013 (http://www.scirp.org/journal/jct)
1085
Plasma Concentrations of Some Trace Element and Heavy
Metals in Patients with Metastatic Colon Cancer*
Ozgur Emre1, Halit Demir1, Erkan Dogan2#, Ramazan Esen3, Tugba Gur4, Canan Demir5,
Edip Gonullu6, Nedim Turan7, Mehmet Fatih Özbay8
1Division of Biochemistry, Department of Chemistry, Science Faculty, Yuzuncu Yil University, Van, Turkey; 2Department of
Medical Oncology, Medical Faculty, Yuzuncu Yil University, Van, Turkey; 3Department of Hematology, Medical Faculty, Yuzuncu
Yil University, Van, Turkey; 4Division of Biochemistry, Health Faculty, Yuzuncu Yil University, Van, Turkey; 5Department of
Biostatics, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey; 6Department of Anesthesiology and Reanimation, Regional
Training and Research Hospital of Van, Van, Turkey; 7Department of Medical Oncology, Faculty of Medicine, Gazi University,
Ankara, Turkey; 8Department of Internal Medicine, Regional Training and Research Hospital of Van, Van, Turkey.
Received June 14th, 2013; revised July 12th, 2013; accepted July 19th, 2013
Copyright © 2013 Ozgur Emre et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Purpose: It is well known that trace elements and heavy metals play a significant role in human health and disease.
These elements play an important role in different metabolic pathways of cells and tissues. Trace element deficiency or
excess is implicated in the development or progression of some cancers. We present a study which investigates serum/
plasma levels of trace-heavy elements in metastatic colon cancer patients and healthy subjects. Methods: Blood sam-
ples were collected from 29 healthy subjects and 40 patients with metastatic colon cancer in Oncology Department of
Medical School of Yuzuncu Yil University. In both groups, the serum levels of copper (Cu), magnesium (Mg), lead
(Pb), chromium (Cr), zinc (Zn) selenium (Se), manganese (Mn), and cadmium (Cd) were determined. Results: Higher
levels of Cu, Mg, Pb, Cr, Zn, Mn and Cd were seen in patients with metastatic colon cancer compared to healthy
subjects and these findings were statistically significant (p < 0.05). Se levels were noted to be lower in patients with
colon cancer in comparison to healthy subjects and this finding was also statistically significant (p < 0.05). Conclusions:
According to our findings there was significant diffence in trace elements and heavy metals levels between healthy sub-
jects and metastatic colon cancer patients. Therefore heavy metal and trace elements may have prognostic significance
in complex disorders including colon cancer. However, further comprehensive studies are needed in order to advance
our understanding of the relationship between heavy metal and trace elements and their role in cancers.
Keywords: Colon Cancer; Trace Element; Heavy Metal; Essential Element
1. Introduction
Colorectal cancer (CRC) is the third most common can-
cer worldwide with an estimated one million new cases
and a half million deaths each year [1,2]. Colorectal can-
cer is thought to result from a complex interaction be-
tween inherited susceptibility and environmental factors,
as indicated by genetics and experimental and epidemic-
ological studies [3-5]. Approximately 75% of patients
have neither a clear family history nor any known pre-
disposing condition [6]. According to observational stud-
ies that had been performed, development of CRC may
be related to environmental factors such as high calorie
intake, high consumption of red meat (especially if over-
cooked), high consumption of saturated fat, low con-
sumption of fruit, vegetables and fibre, high alcohol in-
take, obesity, cigarette smoking, and a sedentary lifestyle
[7]. 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 [8,9].
*Conflict of interest: None. Financial disclosure: None.
#Corresponding author.

Plasma Concentrations of Some Trace Element and Heavy Metals in Patients with Metastatic Colon Cancer
1086
The aim of our study was to investigate the difference
between the serum level of some trace-mineral elements
and heavy metals [copper (Cu), magnesium (Mg), lead
(Pb), chromium (Cr), zinc (Zn), manganese (Mn), cad-
mium (Cd) and selenium (Se)], in patients with colon
cancer and healthy group.
2. Methods
Between May 2008 and September 2010, a total of fourty
patients with metastatic colon cancer and twenty nine
healthy volunteers were enrolled. Venous blood samples
of patients with meastatic colon cancer were obtained
from the antecubital fossa veins in accordance with the
guidelines set out in the Declaration of Helsinki. In-
formed consent was given by all the patients included in
this study. The study was approved by the local ethics
committee. Serum was separated by centrifugation and
the samples were processed immediately. The serum
samples were placed in deionised polyethylene tubes and
kept at −80˚C (without thawing) until samples were ana-
lysed. Determination of serum concentrations of Cu, Mg,
Pb, Cr, Zn, Mn, Cd and Se was performed by Atomic
Absorption Spectrophotometer measurements, in which a
UNICAM-929 spectrophotometer (Unicam Ltd, York
Street, Cambridge, UK) was used.
All statistical analyses were carried out using the
SPSS® statistical software package (SPSS for Windows
version 13.0, SPSS Inc., Chicago, Illinois, USA). The
results were expressed as the Mean ± Standard deviation
(SD). The paired t test was used for normally distributed
variables. Wilcoxon signed rank test was used for vari-
ables that was not normally distributed. A two tailed p
value < 0.05 was considered significant in all tests.
3. Results
In this study, we enrolled a total of fourty patients with
metastatic colon cancer and twenty nine healthy volun-
teers in Oncology Department of Medical School of Yu-
zuncu Yil University. The median age was 67 (range, 45
to 76) years in patients with metastatic colon cancer and
69 (range, 45 to 76) in healthy volunteers. All serum bio-
chemical parametres including hepatic functions of heal-
thy volunteers and test groups were in normal limit.
Among patients with metastatic colon cancer, twenty five
were female and fifteen were male. While, among healthy
volunteers, five of them were female and twenty four of
them were male. Cu, Mg, Pb, Cr, Zn, Mn and Cd value
measured in colon cancer group were higher than the
control group and this was statistically significant (p <
0.05). Se levels were noted to be lower in patients with
colon cancer in comparison to healthy subjects (p <
0.05).
All changes in the serum/plasma level of trace-mineral
elements and heavy metals are summarized in Table 1.
4. Discussion
Malignant tumours arising in the colorectal mucosal epi-
thelium destroy extracellular matrices such as the base-
ment membrane, eventually becoming advanced cancers
metastasising to the liver and other distant organs [10].
Although the risk factors do not fully explain variations
in the incidence of complex disorders generally in cancer
and also colon cancer in particular [11]. Epidemiological
studies that had been performed cause perturbations in
the trace elements in the etiology of a number of diseases
including cancer. Normally the human body does need
materials such as Fe, Zn, Cu, K, Ca, Na, Mg, Mn, Cr, Ni,
Mo, Co and Sn. Toxic concentrations of these com-
pounds can occur due to individual life style, dietary
habits or environmental conditions in the country of ori-
gin. Living organisms have developed mechanisms of
utilising vital trace elements such as Zn and Cu, and re-
ducing the toxic influence of heavy metals like Cd, Hg
and Pb [12].
Cu is a redox-active transition metal that can partici-
pate in single electron reaction and catalyse formation of
free radicals. Beside these properties, it is also an es-
sential element for formation of hemoglobulin, myelin,
collagen, and melanin. Cu has been suggested to play an
important role in several disorders and normal immune
function [13,14]. Nayak et al. performed a study in 20
patients affected by prostate and colon cancer, at the end
of study they found that copper and ceruloplasmin levels
were increased significantly in the cancer patients as
compared to controls. They also speculate that deter-
mination of specific antioxidants (like ceruloplasmin)
Table 1. Serum levels of trace elements and heavy metals in
groups.
Parameter Control group
(X ± SD)
Patients with colon
cancer (X ± SD)
N = 29 N = 40
Cu (mg/L)* 0.151 ± 0.0243 0.241 ± 0.1004
Mg (mg/L)* 10.81 ± 1.4231 32.838 ± 11.8095
Zn (mg/L)* 2.488 ± 0.3332 5.134 ± 1.865
Mn (mg/L)* 0.2862 ± 0.0486 0.3326 ± 0.2063
Cd (mg/L)* 0.0027 ± 0.0003 0.1832 ± 0.1441
Pb (mg/L)* 0.0268 ± 0.0077 0.1788 ± 0.0705
Se (mg/L)* 0.1138 ± 0.0294 0.05534 ± 0.0233
Cr (mg/L)* 0.0061 ± 0.0016 0.0325 ± 0.0080
X ± SD = Mean ± Standard Deviation. *: difference between control group
and patients with metastatic colon cancer is significant (p < 0.05).

Plasma Concentrations of Some Trace Element and Heavy Metals in Patients with Metastatic Colon Cancer 1087
and trace elements (like copper) may be of value in the
early diagnosis of prostate and colon cancer [15]. In our
study, the levels of Cu in patients with colon cancer were
found to be significantly higher. This finding is con-
sistent with Nayak’s study. Therefore, serum Cu determi-
nations may be important while assessing colon cancer
patients.
Magnesium (Mg) is an essential mineral which plays a
role in a number of cellular metabolic reactions. It plays
a role in tumor biology via the regulation of oxidative
stress, carcinogenesis, tumor progression, and angio-
genesis [11,16-18]. It is thought that Mg also plays an
important role in the differentiating cells. Optimal Mg
intake may be prophylactic against initiation of some
neoplasms or cancers. Since cancer cells have high meta-
bolic requirements, it is not indicated (alone) in the treat-
ment of cancer [9,19]. Mg deficiency can paradoxically
increase the risk of, or protect against oncogenesis. Ac
cording to animal studies dietary magnesium may play a
role in the prevention of colorectal cancer, but data in
humans are lacking. Larsson et al. stated that a high mag-
nesium intake may reduce the occurrence of colorectal
cancer in women [20]. In our study, in contrast to these
findings, in patients with colon cancer; a significantly
high level of Mg was detected. Although these results are
challenging with results of previous studies. It should be
kept in mind that previous studies are chemopreventive
type. Therefore role of Mg on cancer formation may be
diffent from role of Mg on cancer that has been already
developped. For explaning this dilemma, further clinical
studies are warranted.
High levels of lead (Pb) exposure cause a number of
negative effects for human health. There is some evi-
dence that suggests lead exposure increases susceptibility
to cancer. Pb may exert diverse toxic effects on cells,
distrupting the ability of cells to develop appropriate and
precise responses to genotoxic environmental agents. It
may also interfere with the ability of DNA to repair itself
after genotoxic insult. By binding histones, Pb may de-
crease the protection these proteins give DNA, directly
increasing the exposure of DNA to damaging agents [21,
22]. In a study conducted by Lustberg M. et al. it was
found that individuals who had high levels of lead had
increased cancer-caused mortality due to lung cancer and
nonlung cancer [23]. According to epidemiological study
that was performed by Gwini et al., among workers ex-
posed to inorganic lead, esophageal cancer was seven-
fold greater among those with a blood lead level result
above 30 μg/dL compared with population rates [24].
These results are consistent with our current study. Com-
pare to the healthy group, Pb levels were significanly
higher in colon cancer patients in our study. Therefore
we think that high level of Pb has impact on development
of colon cancer.
Cr is encountered in every branch of industry. Cr
compounds, when in direct contact with skin and oral
mucosa, can cause allergic dermatitis and skin ulcers.
Teeth and tongue are dyed yellow. It was reported that
via inhalation of dust and fumes, it may result in severe
respiratory tract infections, pneumonia and lung cancer
may occur more specifically with cumulative hexavalent
chromium exposure [25,26]. It is also known that Cr has
carcinogenic effect which occurs by DNA damage through
base pair mutation, deletion, or oxygen radical attack on
DNA [27]. In this study, we found that there was higher
level of Cr in patients with colon cancer compared to
healthy persons. This finding suggests that Cr may play a
role in aetiology of colon cancer.
Zn is a component of many DNA repair proteins. It is
also involved in a variety of general cellular functions
such as cell signal transduction, transcription and replica-
tion [28]. Zn has important role in prevention of cancer
formation by stabilizing the structure of deooxyribonu-
cleic acid (DNA), ribonucleic acid (RNA) and ribosomes.
Animal studies have shown that the administration of Zn
may slow the progression of induced tumours and studies
in humans also show that administration of Zn and other
micronutrients may have therapeutic effects in patients
with oral precancerous lesions [29]. Low serum Zn con-
centrations detected in some cancer such as esophageal
carcinoma, ovarian cancer, cervical cancer [30,31]. By
contrast, high serum level of Zn was detected in liver
cancer [32]. In current study, high serum level of Zn was
detected in patients with colon cancer. Thus, Zn may
play different role in different types of cancers.
Mn is well known as an essential element that is re-
quired for health in trace amounts, but toxic at higher
exposures. During the last decade, Mn has become an
important component of gasoline industy instead of lead.
It is therefore important to evaluate the potential cancer
effects of Mn on the public. Spangler et al. performed an
ecological study for evaluation of potential cancer effects
of Mn and they reported that either groundwater or air
concentrations of Mn is correlated with increase in all-
site cancer rates including colon carcinoma [33]. In our
current study, serum level of Mn was elevated in colon
cancer patients with respect to control healthy group.
Thus we think that high level of Mn might have relation
with colon cancer.
The non-essential heavy metal Cd is a ubiquitous wide
spread industrial and environmental contaminant that
represents hazard to humans and wildlife. It is found in
the air, soil and water and due to its extremely long
half-life, accumulates in plants and animals. The main
source of cadmium exposure for non-smoking human
population is food. On the basis of data from animals and
humans, Cd in food soon becomes absorbed in the blood,
then becomes present in plasma, and later binds to red

Plasma Concentrations of Some Trace Element and Heavy Metals in Patients with Metastatic Colon Cancer
1088
blood cells [34,35]. Cd is established toxic and carcino-
genic metals [36,37]. Cd does not induce direct DNA
damage, however it induces increase in reactive oxygen
species (ROS) formation, which in turn induce DNA
damage and can also interfere with cell signalling. Ac-
cording to epidemilogical studies Cd appears to be asso-
ciated with overall cancer mortality in men and women.
In men, Cd increases risk of lung cancer, pancreatic can-
cer, non-Hodgkin lymphoma and leukemia; while in wo-
men it increases risk of lung cancer, leukemia, ovarian
and uterine cancer but risk of cancer is weaker than in
men [38]. In this study, we found that serum Cd level
was significantly higher in colon cancer patients compare
to healthy group. This finding is important and needs to
be verified with further clinical research.
Se is well known trace element which is involved in
integral parts of antioxidant enzymes such as glutathione
peroxidase [39]. In literature, significantly low serum le-
vel of Se had been detected in patients with prostate
cancer [40,41]. In addition, the report by Clark et al. state
that oral selenium supplementation significantly lowers
incidence of lung, colorectal and prostate cancer [42].
Therefore, Se deficiency may contribute to formation of
many types of malignant neoplasms including colon can-
cer. In our study, Se level was found significantly lower
in colon cancer patients when compared to healthy sub-
jects. Thus, low Se level is most probably related to de-
velopment of colon carcinoma.
In conclusion, environmental factors have an impor-
tant role in pathogenesis of cancer. Therefore heavy me-
tal and trace elements may have prognostic significance
in complex disorders including colon cancer. According
to our results, it is possible that high Se level and low Cu,
Mg, Pb, Cr, Zn, Mn and Cd levels have a protective role
in occurrence of colon cancer.
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doi:10.1001/jama.1996.03540240035027

Plasma Concentrations of Some Trace Element and Heavy Metals in Patients with Metastatic Colon Cancer
1090
Abbreviation
Copper (Cu)
Magnesium (Mg)
Zinc (Zn)
Manganese (Mn)
Cadmium (Cd)
Lead (Pb)
Selenium (Se)
Chromium (Cr)