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Background: Colorectal cancer (CRC) is considered the fourth type of cancer that causes death in the world. Changes in levels of Zinc (Zn), Copper (Cu), and Selenium (Se) as well as low glutathione peroxidase (GPx) activity can lead to CRC and this study was aimed to evaluate their possible use as diagnostic markers. Methods: CRC patients (n=90) were divided into three groups; newly diagnosed, before surgery, and after surgery. These groups were compared to healthy subjects (n=30); the mean age ±SD was 50.63±9.26 and 49.97 ±10.85 for CRC patients and healthy subjects, respectively. Biochemical study for serum levels of Zn and Cu were measured by FAAS, Se was measured by HGAAS, and ELISA for GPx. Results: Zn, Cu, Se and GPx were significantly lower in all CRC patient groups, except for the after surgery group which showed no differences for Zn and GPx as compared to the healthy subjects. Positive correlations were found between Se and Zn and between Se and GPx (r = 0.71, r = 0.42; P < 0.01, respectively) in all CRC patient groups. A receiver operating characteristic (ROC) curve analysis applied for the newly diagnostic group showed that all parameters can be used as diagnostic markers for CRC. Conclusion: The present results conclude that Zn, Cu Se, and GPx can be used as diagnostic markers for CRC, where the decrease of these parameters may be associated with an increased risk of CRC and as indicators of the response to therapy.
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Caspian J Intern Med 2020; 11(4):384-390
DOI: 10.22088/cjim.11.4.384
Original Article
Copyright © 2020, Babol University of Medical Sciences
This open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0
Raghad F. Al-ansari (MSc) 1
Abdulnasser M. AL-Gebori
(PhD) 1
Ghassan M. Sulaiman (PhD) 2*
1. Applied Chemistry Division,
Applied Science Department,
University of Technology,
Baghdad, Iraq
2. Biotechnology Division, Applied
Science Department, University of
Technology, Baghdad, Iraq
* Correspondence:
Ghassan M. Sulaiman,
Biotechnology Division, Applied
Science Department, University of
Technology, Baghdad, Iraq
E-mail: gmsbiotech@hotmail.com
Tel: 0096 49702781890
Received: 15 Sep 2019
Revised: 9 Feb 2020
Accepted: 16 Feb 2020
Serum levels of zinc, copper, selenium and glutathione
peroxidase in the different groups of colorectal cancer patients
Abstract
Background: Colorectal cancer (CRC) is considered the fourth type of cancer that causes
death worldwide. Changes in the levels of zinc (Zn), copper (Cu), and selenium (Se) as well
as low glutathione peroxidase (GPx) activity can lead to CRC and this study was aimed to
evaluate their possible use as diagnostic markers.
Methods: CRC patients (n=90) were divided into three groups; newly diagnosed, before
surgery, and after surgery. These groups were compared to healthy subjects (n=30); the
mean age ±SD was 50.63±9.26 and 49.97±10.85 for CRC patients and healthy subjects,
respectively. Biochemical study for serum levels of Zn and Cu was measured by FAAS, Se
was measured by HGAAS, and ELISA for GPx.
Results: Zn, Cu, Se and GPx were significantly lower in all CRC patient groups, except for
the after surgery group which showed no differences for Zn and GPx as compared to the
healthy subjects. Positive correlations were found between Se and Zn and between Se and
GPx (r=0.71, r=0.42; P<0.01, respectively) in all CRC patient groups. A receiver operating
characteristic (ROC) curve analysis was applied for the newly diagnostic group showing all
the parameters that can be used as diagnostic markers for CRC.
Conclusion: The present results conclude that Zn, Cu Se, and GPx can be used as diagnostic
markers for CRC, where the decrease of these parameters may be associated with an
increased risk of CRC and as indicators of the response to therapy.
Keywords: Colorectal cancer, Zn, Cu, Se, GPx, Serum.
Citation:
Al-ansari R, Al-Gebori A, Sulaiman G. Serum levels of zinc, copper, selenium and glutathione
peroxidase in the different groups of colorectal cancer patients. Caspian J Intern Med 2020; 11(4):
384-390.
Colorectal cancer (CRC) is considered as the fourth cause of death among types of
cancer globally. It is also ranked third among the most commonly diagnosed types of cancer
(1). CRC refers to malignant epithelial neoplasms that occur in the colon and/or the rectum
by transforming epithelial cells into adenocarcinoma cells (2). Zinc (Zn), copper (Cu), and
selenium (Se) are essential dietary nutrients for the body and are implicated in cancer risk, where
they act as anti-oxidant agents. Zn catalyzes the activity of more than 300 enzymes and has roles
in the immune function, DNA synthesis, protein synthesis, and cell division. It is also
responsible for the maintenance of the structure of DNA and its binding to more than 1000
transcription factors that are required for gene expression of many proteins. Cu plays an
important function in preserving the integrity of DNA by preventing oxidative DNA damage.
Many enzymes and proteins in humans depend on Zn, Cu and Se. Both Zn and Cu play the
main role in the activity of the antioxidant enzyme known as copper-zinc superoxide dismutase.
Se also contributes to the formation of some enzymes such as glutathione peroxidase (GPx),
thioredoxin reductase (TrxR) and iodothyronine deiodinases (IDD) which act as anti-oxidant
enzymes.
Caspian J Intern Med 2020; 11(4): 384-390
Trace elements and glutathione peroxidase in serum of colorectal cancer patients 385
It has also an important role in the protection against
oxidative stress through the action of antioxidant
selenoproteins against reactive oxygen species (ROS) and
reactive nitrogen species (NOS). Together, H2O2, O2−, and OH
radicals form the ROS, the excessive generation of which
causes oxidative stress. Many diseases, such as cancer, can
develop as a result of oxidative stress, if there is an imbalance
between the defense antioxidant system of the cell and the
generation of ROS species (3-8).
A previous study on CRC patients showed that the serum
level of Se decreased while Zn level increased, while it
showed no difference in the level of Cu (9). Zn deficiency
appeared in colon cancer patients, whereas Cu showed no
difference compared with the healthy controls in a Saudi
population (10). Iraqi patients with colon cancer also showed
a decrease in Zn and an increase in Cu levels (11). The same
findings were also reported in CRC patients in Brazil (12).
Another recent study has reported that both Zn and Cu
decreased in Iranian CRC patients (13).
GPx (EC 1.11.1.9) is an enzyme that is classified as
oxidoreductase which catalyzes the reduction of the organic
hydroperoxides or H2O2 to corresponding alcohols or water
using reduced glutathione. Some GPx isozymes are described
as selenium-dependent (14). Previous studies reported that
GPx activity in colon cancer patients was lower in the plasma
and serum as compared to the control (15, 16).
Several factors are involved in the process of CRC
treatment, including the disease stage; about 95% of stage I
and 65-80% of stage II patients can only be treated via
surgery. However, several types of treatment such as chemo-
and radiotherapy can be applied to patients in stages III and
IV before having to undergo surgery (17). The ability of
cancer cells to spread to other tissues, including lymph nodes,
was well documented, while the rate of this process as well as
the speed of cancer cells growth are correlated with the
disease grades that are classified into G1, G2, and G3
according to severity (18).
Hence, the previous investigations conducted on the
relationships between Zn and Cu with CRC are controversial
as to whether these elements increased or decreased in the
serum of the patients. Also, the cutoff values of these
parameters were not defined by previous studies. In this study,
we assessed the levels of these parameters in different groups
of CRC patients and determined the cutoff values that could
be applied for newly diagnostic patients. Also, we analyzed
the correlations among the investigated elements.
Methods
Study population: This research involved 30 healthy subjects
(males and females) and 90 patients who were diagnosed as
primary colorectal adenocarcinoma patients. The mean age
was 49.97 ±10.85 years for healthy subjects and 50.63±9.26
years for CRC patients. Healthy subjects matched the patients
in the gender ratio. Tumor lymph node metastasis (TNM)
system was used for staging. CRC patients were divided into
three equal groups; newly diagnosed (no treatment, no
surgery, all stages of disease), before surgery (chemo- and
radiotherapy-treated, stages III and IV), and after surgery (No
treatment before and after surgery, stages I and II). Patients
with diabetes, heart diseases, kidney failure, familial history
for CRC, intestinal polyposis, chronic digestive problems, and
those who are alcoholic and smokers were excluded. The
diagnosis for CRC patient was performed by consultant
doctors who identified tumor location, whereas tumor type,
grade, and stage were identified by pathologists. The ethics
committee of the Medical City in Baghdad, Iraq approved this
research. The number of CRC patients within stage I was 23
(25.55%), stage II was 23 (25.55%), stage III was 22
(24.44%), and stage IV was 22 (24.44%). The number of
patients with grade 1 was 22 (22.22%), grade 2 was 58 (64.44
%), and grade 3 was 12 (13.33%). Tumor location was
determined using the International Classification of Diseases
(ICD- version 10). Patients with colon and those with rectal
cancers were both included, where the number of patients who
had a primary tumor in the cecum was 4 (4.44%), in the
ascending colon,11 (12.22%), in the hepatic flexure,5
(5.55%), in the transverse colon, 8 (8.88%), in the splenic
flexure, 6 (6.66%), in the descending colon, 15 (16.66%), in
the sigmoid colon, 12 (13.33%), in the recto-sigmoid junction,
10 (11.11%), and in the rectum was 19 (21.11%).
Materials: Chemicals used for preparing standard solutions
of Zn, Cu and Se element were purchased from Merck KGaA,
Germany. Enzyme linked immunosorbent assay research kit
(type sandwich ELISA) was used to assay glutathione
peroxidase activity purchased from MyBioSource-U.S.A.
Laboratory assessment: Specimens were taken from healthy
subjects and CRC patients; Blood (10 mL) was collected from
each person, then the serum was stored at -40º C after being
separated by centrifugation. Atomic absorption spectroscopy
(AAS; novAA 300, Analytik Jena, Germany) was used to
assay Zn, Cu and Se, whereas flame atomic absorption
spectroscopy (FAAS) was used for Zn and Cu assay, using
acetyleneair as a flame and hollow cathode lamps as a
Caspian J Intern Med 2020; 11(4): 384-390
386 Al-ansari RF, et al.
radiation source. Burner height and gas flow rates were
adjusted to achieve the highest absorbance signal of each
element. Slit width used to isolate wavelength was 1 nm.
Absorbance was read at 213.9 nm and 324.7 nm, respectively,
for Zn and Cu. Hydride generation atomic absorption
spectroscopy (HGAAS) was used for Se assay. Hydride
generation system was heated to 950º C. Absorbance was read
at 196.0 nm. Carrier gas was argon. For hydride generation,
NaBH4 0.6% solution (98% Sigma, Germany) in 0.6% NaOH
(HiMedia Laboratories Pvt. Ltd., India) was prepared.
Samples were prepared by adding 3 mL of HNO3 70%
(HiMedia Laboratories Pvt. Ltd., India) to 1 mL of serum,
followed by decomposition by microwave according to a
specific program for decomposition. Samples were then left
for 10 min before adding deionized water to a defined volume.
These steps were applied to all samples. 5 mL of HCl 37%
(Sigma, Germany) was also added to samples prepared for the
Se assay which were heated at 85º C for 30 min (9).
Statistical analysis: IBM SPSS statistics Version 24 was used
to analyze the data by Windows 10. The parameters were
expressed as mean±SD, for normal distribution Shapiro- Wilk
test was used and for homogeneity of variance, Levene test
was used, One-way ANOVA test was used to find the
differences in the means between the groups also t-test. The
cutoff values and diagnostic markers were estimated by
receiving operating characteristic (ROC) curve. The Pearson
correlation coefficient was used to find the correlations among
the parameters. Differences at p<0.05 were considered to be
significant.
Results
The values of all the tested parameters (Zn, Cu, Se and
GPx) were significantly lower in all CRC patient groups as
compared to healthy subjects, except for the after surgery
group which showed no significant difference for Zn and GPx
table 1. Age (years) showed no differences between CRC
patient groups, newly diagnosed, before and after surgery,
(50.75±11.93, 52.00±12.79, and 49.16±12.08; respectively)
compared with healthy subjects (49.97±10.85). Body mass
index (Kg/m2) also showed no differences between CRC
patient groups (23.94±3.50, 24.18±4.55, and 24.02±4.03;
respectively) compared with healthy subjects (24.12±2.34).
The correlations among the parameters are shown in table 2,
while the positive correlations between Se and Zn and
between Se and GPx are shown in figures 1 and 2.
ROC curve analysis was applied for the newly diagnostic
group and showed that Zn, Cu, Se, and GPx can be used as
diagnostic markers for CRC disease; the area under the curve
(AUC) explains the ability of using these parameters as
markers. The analysis showed that all the differences in the
AUC values were significant (p<0.01). For each parameter,
95%-confidence interval (95%-CI) and standard error (SE) for
the AUC were calculated. The cutoff values were assessed at
the maximum of both sensitivity and specificity, as shown in
table 3.
Correlations between both BMI and age with the
parameters in healthy subjects and CRC patients are shown in
table 4. The associations of clinical features for CRC patients
and the parameters are shown in table 5.
Table 1. Total mean serum levels of Zn, Cu, and Se, with GPx activity in the sera of healthy subjects and CRC patients
Groups
Zn (μg/dL)
Mean±SD
Cu (μg/dL)
Mean±SD
Se (μg/dL)
Mean±SD
GPx (U/L)
Mean±SD
Healthy subjects
98.97±4.78
80.11±3.21
136.03±4.23
Newly diagnosed
69.37±3.72**
30.38±2.57**
69.73±4.94**
Before surgery
78.43±5.01**
47.55±3.35**
98.35±3.63**
After surgery
101.23±5.32
55.50±2.48*
133.78±5.10
*P<0.05, **P<0.01
Table 2 .Correlations between parameters in serum for CRC patients
Correlation between
r (P-value)
Zn and Cu
-0.16 (>0.05)
Zn and Se
0.71 (<0.01)
Zn and GPx
0.24 (>0.05)
Cu and Se
0.01 (>0.05)
Cu and GPx
-0.07 (>0.05)
Se and GPx
0.42 (<0.01)
Caspian J Intern Med 2020; 11(4): 384-390
Trace elements and glutathione peroxidase in serum of colorectal cancer patients 387
Figure 1: Positive correlation between Se and Zn in
CRC patients.
Figure 2: Positive correlation between Se and GPx in
CRC patients.
Table 3. ROC curve analysis findings for parameters.
Parameters
AUC
SE
Sensitivity (%)
Specificity (%)
95% - CI
Cutoff value
Zn
0.91 *
0.04
89
69
0.82- 1.00
84.45 (μg/dL)
Cu
1.00 *
0.00
100
0
1.00- 1.00
55.24 (μg/dL)
Se
1.00 *
0.00
100
0
1.00- 1.00
5.40 (μg/dL)
GPx
0.91 *
0.05
78
84
0.80- 1.00
113.37 (U/L)
* P<0.01
Table 4. Correlations between both BMI and age with parameters in serum for healthy subjects and CRC patients
Correlation between
CRC Patients
r (p value)
Healthy subjects
r (P-value)
Zn and Age
0.03 (0.75)
-0.14 (0.53)
Cu and Age
-0.09 (0.43)
0.08 (0.73)
Se and Age
-0.005 (0.96)
0.18 (0.44)
GPx and Age
0.02 (0.87)
-0.29 (0.20)
Zn and BMI
-0.01 (0.93)
-0.22 (0.33)
Cu and BMI
-0.08 (0.50)
-0.03 (0.10)
Se and BMI
0.25 (0.04)
0.27 (0.26)
GPx and BMI
-0.01 (0.90)
0.04 (0.86)
Table 5. Association of clinical features for all CRC patients and serum levels of Zn, Cu, Se, and GPx
Group
Case (%)
Zn (μg/dL)
Mean±SD
Cu (μg/dL)
Mean±SD
Se (μg/dL)
Mean±SD
GPx (U/L)
Mean±SD
Sig.
Gender
Female
Male
48.88
51.11
82.77±2.32
83.23±1.34
45.91±1.86
43.02±3.69
4.99±0.4
5.03±0.5
98.98±3.56
102.22±4.43
N.S
Age
≤50
>50
52.22
47.77
81.87±5.04
84.13±4.43
45.70±3.76
43.22±2.34
5.03±0.6
4.99±0.3
99.37±3.56
101.95±2.43
N.S
Therapy*
Without
With
50.00
50.00
69.37±3.72
78.43±5.01
30.38±2.57
47.55±3.35
2.87±0.56
4.77±1.06
69.73±4.94
98.35±3.63
<0.001
*Only between two groups of CRC patients (the newly diagnosed and the before surgery). N.S: Non-significant
Caspian J Intern Med 2020; 11(4): 384-390
388 Al-ansari RF, et al.
Discussion
Alterations of trace element levels adversely affect many
biological processes and they could also promote
carcinogenesis. The results of our study showed that Zn, Cu,
Se and GPx were significantly lower in all groups of CRC
patients, while the patients in the after surgery group showed
no significant difference for both Zn and GPx, as shown in
table 1.
In the present study, all groups of CRC patients were
deficient in Cu and Se, as it was observed, for example, in the
newly diagnosed group in all stages as well as in the patients
before surgery who received radiotherapy and chemotherapy
in advanced stages. In the after surgery group, the early
surgical intervention in the patients with eral stage disease
could not restore normal levels of the studied elements, even
after 21 days of post-surgical blood collection. This indicates
that tumor removal was not efficient in bringing these
parameters to normal levels. A recent study on males and
female patients with thyroid cancer has demonstrated that
serum levels of Se significantly decreased in the pre- and post-
operative patients, an effect that was suggested to be
associated with thyroid cancer pathogenesis (19).
The rise in the levels of free radicals was related to cancer
etiology because such a rise can damage DNA, cause
destruction of proteins, and ultimately lead to tumor growth.
Copper-restricted diet in humans leads to elevated fecal free
radicals, and causes cytotoxicity which is one of the putative
colon cancer’s risk factors (20-23).
Moreover, experiments in animals indicated that low Cu
intake is considered as a risk factor for 3,2’-dimethyl-4-
aminobiphenyl (DMABP)-induced colon tumor development
in rats, whereas the activities of ceruloplasmin and Cu,Zn-
SOD enzymes were reduced in rats fed on low Cu intake (24).
Se is engaged in a number of biochemical pathways where it
can be found in many forms. Anticarcinogenic pathways of
Se include the prevention of oxidative damage, regulation of
immune responses, repair of DNA damage, and regulation of
apoptosis and cell cycle (25, 26). Selenomethionine is a major
component of Se diet that modulates the redox status
(reduction/oxidation) (20, 27). Besides that, it induces the
P53-mediated cell cycle arrest and programmed cell death in
human colon cancer cells (28). Se significantly induces
apoptosis and its relatively high doses were related to
overexpression of p53 in rat hepatocytes (29). A previous
study reported that low serum levels of Se were strongly
correlated with CRC risk (30). Zn level and GPx activity
significantly decreased in the newly diagnosed and before
surgery groups, but the levels showed non-significant
differences in the after surgery group as compared with
healthy subjects. This may be attributed to the stage and
differentiation grade of the disease. Our study with the after
surgery group involved patients in G1 and G2 grades only,
that showed non-significant difference in these parameters as
compared to the control group.
In a study conducted on colon and rectal cancer patients of
all stages of the disease who did not undergo surgical
intervention or treatment, the authors reported that the levels
of serum Zn significantly decreased but only in advanced
stages (31).
Another study in patients with colon and stomach cancer
demonstrated that high grade differentiated (G3; poorly
differentiated) stomach tissue has lower Zn level comparing
with the normal tissue and with the tissues from moderately
differentiated carcinoma G2 and well-differentiated
carcinoma G1 grades. Also, the study reported the inverse
association between Zn levels in the tissues and the advanced
stages of carcinoma in both colon and stomach cancer patients
(32). In our study, ROC curve analysis for the newly
diagnosed group was used to illustrate the association of these
parameters with CRC. The findings in table 3 indicate that the
parameters can be used as diagnostic markers, where a very
highly significant difference in AUC is shown. These values
can be used to predict people's health when the levels of these
parameters are less than the cutoff values, then the individuals
are at risk or already having CRC. A previous study noted that
the progression to colon cancer was associated with low levels
of Zn and decreased Cu,Zn-SOD activity in the plasma of rats
(33). P53 folding and misfolding is modulated by Zn, which
is one of the reasons that causes cancer (34). A previous study
about colorectal cancer showed that the serum levels of both
Zn and Cu were significantly lower as compared to healthy
people (13). Human CRC patients had lower serum
concentrations of Cu, Zn, and Se according to a review
published in 2019 (35). Our results are consistent with these
studies. Cu and Zn deficiencies have recently increased in
different regions of the world for unknown reasons. The total
prevalence of Cu deficiency in populations in Iran and Spain
was 32.1 % (age 15-65 years old) and 30.1 % (age over 60
years old), respectively. The Spanish study also reported that
the total prevalence of Zn deficiency was 66.8% (36, 37). The
positive correlation between Zn and Se that we found can be
explained by the results of a previous report which found that
Caspian J Intern Med 2020; 11(4): 384-390
Trace elements and glutathione peroxidase in serum of colorectal cancer patients 389
Zn can induce a decrease in Se urinary excretion (38). In a
previous study on humans, two significant positive
correlations between Zn and Se were found in two biological
media (urine and feces) from healthy people. The study also
found a significant positive correlation between dietary Zn
intake and Se levels in blood (39). Hence, Zn deficiency may
contribute to Se deficiency. Hypothetically, Zn may influence
the status of Se by modulating one of the phases of Se
homeostasis, represented by absorption, excretion or
retention. We also found another correlation between Se and
GPx, where Se deficiency led to decreased GPx activity,
which was previously shown to result in the accumulation of
H2O2, leading to destruction of the cells (14,5). In studies
conducted on colon cancer patients, the GPx activity was
reported to decrease in the plasma and serum (15, 16). Our
results have been consistent with these recent studies.
In our study, BMI was positively associated with serum Se
levels in CRC patients. A previous study found that high Se
diet causes a subclinical hypothyroid response which leads to
weight gain and decreases energy expenditure. But a low Se
diet causes a subclinical hyperthyroid response which leads to
weight loss and increases energy expenditure. Therefore,
dietary Se intake alters the energy metabolism of humans
(40). Other parameters showed no association with BMI for
all CRC patients groups, including patients under treatment.
In a previous study on breast cancer, the patients showed a
BMI that was not affected by therapy (41).
In conclusions our findings indicate the involvement of
low levels of Zn, Cu, and Se as well as the low activity of GPx
in the pathogenicity of CRC. Zn level and GPx activity
significantly decreased in the newly diagnosed and before
surgery groups, but not in the after surgery group. This may
be attributed to the stage and differentiation grade of the
disease. Such low levels were not observed in the control
subjects, while the applied exclusion criteria could probably
exclude other possible sources of such declined levels, which
confirm the strict association between CRC and these
parameters. Thus, we conclude that Zn, Cu Se, and GPx can
be used as diagnostic markers for CRC, where the decrease of
these parameters may be associated with an increased risk of
CRC and as indicators of the response to therapy.
Acknowledgments
We thank the patients and healthy volunteers for their
support and participation in this research study and the staff
of the Medical City-Ministry of Health and Environment,
Baghdad, Iraq for their assistance.
Conflicts of interest: There are no conflicts of interest.
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... Colorectal cancer (CRC) is one of the most common malignancies worldwide for both sexes. CRC most frequently originates from a precancerous lesion such as an adenomatous polyp, i.e., a colorectal adenoma (CRA) [1][2][3]. Selenium (Se), zinc (Zn), and copper (Cu) are considered to be involved in carcinogenesis, including in the colon, through various mechanisms. All three trace elements indirectly participate in the defence against reactive oxygen species (ROS) [3][4][5]. ...
... Selenium (Se), zinc (Zn), and copper (Cu) are considered to be involved in carcinogenesis, including in the colon, through various mechanisms. All three trace elements indirectly participate in the defence against reactive oxygen species (ROS) [3][4][5]. Selenoproteins mainly mediate the biological functions of Se. Approximately half of all functionally characterised seleno-death has been discovered which results from excessive copper levels. ...
... It was demonstrated that Cu is crucial for angiogenesis, inter alia, due to the activity of such factors as the vascular endothelial growth factor (VEGF), interleukin-1, and the basic fibroblast growth factor [28]. An increased Cu concentration in serum and tissue was detected in various cancers, including in the gastrointestinal tract, but contradictory data was also published [3,29,30]. ...
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Selenium (Se), zinc (Zn), and copper (Cu) are known to be involved in carcinogenesis and participate in the defence against reactive oxygen species (ROS). This study aimed to evaluate the clinical utility of serum Se, Zn, and Cu concentrations and plasma total antioxidant status (TAS) in the diagnosis of colorectal cancer (CRC) and colorectal adenoma (CRA) in a population of low Se and borderline Zn status. Based on clinical examination and colonoscopy/histopathology, the patients (n = 79) were divided into three groups: colorectal cancer (n = 30), colorectal adenoma (n = 19), and controls (CONTROL, n = 30). The serum Se concentration was lower in the CRC group than in the CRA group (by 9.1%, p < 0.0001) and the CONTROL group (by 7.9%, p < 0.0001). In turn, the serum Zn concentration was decreased in the CRA group (by 17.9%, p = 0.019) when compared to the CONTROL group. Plasma TAS was lower in the CRC group (by 27.8%, p = 0.017) than in the CONTROL group. In turn, the serum Zn concentration was decreased in the CRA group when compared to the CONTROL group. Plasma TAS was lower in the CRC group than in the CONTROL group. ROC (receiver operating characteristic) curve analysis revealed that the Se level was of the highest diagnostic utility for the discrimination of the CRC group from both the CRA group (area under ROC curve (AUC) 0.958, sensitivity 84.21%, specificity 100%) and the CONTROL group (AUC 0.873, sensitivity 100%, specificity 66.67%). The Zn and TAS levels were significantly accurate in the differentiation between the groups. An individualised risk of colorectal adenoma and cancer approach could comprise Se, Zn, and TAS assays in the population.
... It helps maintain the structure and function of these proteins, ensuring that they can correctly identify and correct errors in the DNA sequence [10]. Similarly, selenium is involved in the maintenance of endogenous antioxidant systems like glutathione peroxidase, which protect DNA from oxidative damage and help in maintaining genomic stability [11]. Vitamin B complex, particularly folate (vitamin B9), is critical for the synthesis and repair of DNA. ...
... Zinc supports DNA repair enzymes, maintaining their function in correcting DNA errors [10], while selenium and Vitamin B complex, especially folate, help protect and repair DNA [11]. Folate, for example, is essential for DNA synthesis and repair, and its supplementation can reduce cancer risks linked to DNA damage [13]. ...
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Cancer remains a leading cause of morbidity and mortality worldwide, necessitating ongoing exploration of effective prevention strategies. Micronutrients, vital for maintaining cellular health, offer promising avenues for cancer prevention. This review delineates the critical roles of micronutrients in cancer prevention, elucidating their mechanisms at the cellular level. Focusing on essential vitamins and minerals like Vitamins A, C, D, E, selenium, and zinc, we explore their profound effects on fundamental cellular processes such as DNA repair, oxidative stress regulation, cellular proliferation, and immune surveillance. These nutrients, characterized by their antioxidative, anti-inflammatory, and immune-enhancing properties, have shown potential in reducing the risk of cancer. The article synthesizes outcomes from a broad spectrum of clinical trials, epidemiological studies, and systematic reviews to evaluate the efficacy of micronutrients in thwarting cancer development. This critical analysis explores significant trials, addresses controversies in nutrient efficacy, and highlights the implications for clinical practice and public health policy. The review underscores the importance of integrating nutritional strategies into comprehensive cancer prevention frameworks and suggests directions for future research to optimize the preventive potentials of micronutrients.
... As a result, the relationship between trace elements and cancer is receiving increased attention. Several investigations for colorectal cancer [54], cancers of the bladder [55], thyroid [56], breast [19], endometrium and ovary [16], and oral [22] 2). We did not find any substantial connections between zinc and ovarian cancer risk without any significant risk differences in blood levels of zinc. ...
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Objective: To estimate and compare the levels of zinc in the blood of ovarian and breast cancer patients with those in healthy individuals in the Gujranwala Division, Pakistan. Methods: This study included 67 breast cancer patients, 36 ovarian cancer patients, and 26 healthy controls. Various demographic features were considered: age, BMI, marital status, family history, cancer stage, tumour stage, grades, and lymph nodes. Blood samples were analysed using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) to determine zinc concentration. Categorical sociodemographic data were analysed using the Chi-Square test, while continuous data (zinc concentration) were examined using the Wilcoxon rank test. Results: Zinc levels were evaluated to assess their association with breast and ovarian cancer risk. The zinc level in breast cancer patients (1.5481 ± 0.67175 ppm) and ovarian cancer patients (1.9020 ± 1.21057 ppm) showed no significant difference compared to the control group (1.5346 ± 0.46528 ppm). Additionally, zinc levels exhibited no significant association with the sociodemographic data. Interestingly, a subgroup analysis revealed that postmenopausal breast cancer patients exhibited slightly elevated zinc levels compared to premenopausal patients, although this difference was not statistically significant. Furthermore, patients with advanced-stage ovarian cancer demonstrated a minor, non-significant increase in zinc levels compared to those with early-stage disease. Conclusion: The study concludes that women with breast and ovarian cancer do not exhibit significantly different blood zinc levels compared to healthy controls. However, minor variations in zinc levels among different subgroups suggest the need for further investigation into the potential role of zinc in cancer progression and prognosis.
... These findings agree with studies that concluded significantly elevation of SOD in colorectal patients compared to the control group (Zińczuk, et al., 2019b) and (Balaky, 2023). A study by (Al-Ansari, Al-Gebori, and Sulaiman, 2020) concluded that values of all the tested (GPx) in blood samples were significantly lower in all CRC patient groups as compared to healthy subjects. A study carried out at the Medical University in Łódź affirmed a notable rise in GPx and SOD (p < 0.05) among patients in comparison to the healthy control group (Malinowska, et al., 2015). ...
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Colorectal cancer (CRC), a global health challenge, exhibits rising incidence in low-income nations due to lifestyle changes. Oxidative stress, indicated by reactive oxygen species imbalance and Malondialdehyde (MDA), is linked to CRC. This study investigates oxidative stress markers, antioxidant enzymes, genetic markers, cellular regulation markers, and Vitamin E in CRC patients in Erbil. Ninety CRC patients and 30 healthy controls provided blood samples, processed and stored at –20°C. Enzyme-linked immunosorbent assay kits quantified oxidative stress, antioxidant markers, and Vitamin E. Oxidative stress markers showed significant differences, with elevated MDA and 8-hydroxy-2’-deoxyguanosine levels in patients. Nitrotyrosine exhibited lower expression in patients. Antioxidant enzymes glutathione peroxidase and superoxide dismutase were enhanced in patients, while glutathione (GSH), glutathione reductase and catalase levels were significantly lower in patients. The genetic marker KRAS showed a substantial decrease in patients (<0.0001) but both adenomatous polyposis coli (APC) and CRC antigen (CCA) were higher. Serum vitamin E levels were significantly lower in patients (71.78 ± 6.368) compared to controls (142.3 ± 4.828, p < 0.0001). Elevated oxidative stress, altered enzymatic activity, significantly lower expression of KRAS, and higher expression of APC and CCA in the patient group. Furthermore, reduced Vitamin E levels were observed in the patient group, highlighting potential challenges in antioxidant defense.
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The objective of the present study was to assess serum and cancerous tissue biometal levels in colorectal cancer (CRC) patients, and its relation to disease severity. A total of 90 CRC patients and 97 controls were involved in the present study. The level of biometals in blood serum and colon tissues (only in CRC cases) was evaluated by inductively-coupled plasma mass-spectrometry. CRC patients are characterized by lower serum Ca, Fe, Se, and Zn, as well as higher serum Co, Cu, Mg, V, and Cu/Zn ratio compared to healthy controls. The lowest serum Zn levels and the highest Cu concentration and Cu/Zn ratio were observed in patients with the largest tumor size. Regression analysis demonstrated that tumor size is a significant negative predictor of serum Se levels, being positively associated with serum Cu/Zn values. The degree of metastasis to regional lymph nodes was inversely associated with circulating Ca, Co, Mg, Zn, and Mn levels. Serum Mg and Mn levels were positively associated with the stage of the disease and tumor location, respectively. Cancerous tissue Ca and Mo levels were lower, while Mg content was higher compared to healthy adjacent tissues. In cancerous tissues a constant but non-significant trend to elevation of tissue Zn content with increasing tumor size was observed. In addition, serum Cu, Zn, and Cu/Zn values positively correlated with the respective tumor values. These findings demonstrate that altered biometal metabolism is associated with CRC, while systemic Cu/Zn ratio may be indicative of Cu and Zn imbalance in cancerous tissue.
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Introduction: There is ample evidence regarding the protective effects of antioxidant vitamins and minerals against oxidative stress. The discovery of zinc's protective role in countering free-radical formation and oxidative stress has instigated extensive research into the antioxidant properties of zinc and its involvement in the antioxidant defense system. Furthermore, the utilization of plants with antioxidant properties has gained increasing attention among researchers. This study aims to investigate the impact of six weeks of aerobic exercise training, along with supplementation of pumpkin seed oil and chickpeas, on the gene expression of antioxidant enzymes in the liver and muscle tissues of male rats. Materials & Methods: To achieve this objective, 36 Wistar rats were divided into six groups: control (C), training (T), chickpea (Ch), chickpea + training (Ch+T), pumpkin seed oil (P), and pumpkin seed oil + training (P+T). At the conclusion of the training and supplementation period, the gene expression of the antioxidant enzymes glutathione peroxidase 1 (GPX1) and catalase (CAT) were assessed. Data were subjected to one-way analysis of variance at a significance level of P < 0.05. Results: The results revealed that in all the groups involving pumpkin seed oil and chickpea supplementation, in both liver and muscle tissues, a nonsignificant decrease in the expression of the enzymes CAT and GPX1 was observed when compared to the control and exercise training groups. Conclusion: To a certain extent, the use of pumpkin seed oil and chickpeas may enhance the expression of antioxidant enzymes
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سرطان القولون والمستقيم هو اضطراب يبدأ حصريا في القولون والمستقيم وينجم عن تكاثر الشاذ للخلايا الظهارية الغدية في القولون. من المعلوم أن مستضد الكربوهيدرات 19-9 والمستضد السرطانى المضغى والكالسيوم والزنك يلعبون دورا هاما فى امراض ورم القولون والمستقيم. الهدف من هذه الدراسة هو التحقيق في مستويات مصل لمستضد الكربوهيدرات 19-9 و المستضد السرطاني المضغي والكالسيوم والزنك فى مرضى سرطان القولون والمستقيم. في هذه الدراسة تم البحث عن الأهمية الحيوية لمستضد الكربوهيدرات 19-9 ومستضد السرطاني المضغي والكالسيوم والزنك في تطور السرطان من خلال مقارنة مستويات مصل مرضى المصابين بسرطان القولون والمستقيم مع مجموعة الاصحاء في مستشفى ناناكالي في اربيل. تم فحص مستويات مستضد الكربوهيدرات 19-9 و مستضد المصل السرطاني المضغي و الكالسيوم والزنك في 50 مريضا مصابا بسرطان القو لون والمستقيم و 50 من مجموعة الاصحاء. تم العثور على علاقة أيجابية كبیرة بين المستضد الكربوهيدرات 19-9 ومستضد السرطانى المضغي.( P<0.0165, r= 0.37230) و ارتباط سلبي غير معنوي بين المستضد الكربوهيدرات 19-9 مع الكالسيوم (P=0.77, r= -0.0471) والزنك .(P=0.6334r= -0.07676) وفقا لهذه الدراسة ، هناك علاقة مباشرة بين سرطان القولون والمستقيم ومستويات مصل الدم لكل من مستضد الكربوهيدرات 19-9 ، مستضد السرطانى المضغي ، الكالسيوم والزنك. و تظهر النتائج بشكل ملحوظ القيمة العالية لمصل المستضد الكربوهيدرات 19- 9 (p<0.0001) و مستضد السرطانى المضغي P<0.0001)) و انخفاض كبير في قيم كل من الكالسيوم 0.0011) ( والزنك (0.0046) في مرضى سرطان القولون والمستقيم عند مقارنتها بمجموعة الاصحاء. النتائج التي توصلنا اليها تظهر ان زيادة مستويات المستضد الكربوهيدرات 19-9 ومستضد السرطاني المضغي و انخفاض مستويات الكالسيوم والزنك يمكن ان التسبب في ظهورسرطان القولون والمستقيم وتطوره.
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Background Trace elements play a pivotal role in Colorectal Cancer (CRC) inhibition and development process. This systematic review provides the basic comparison of case-control studies focusing on concentration of trace elements between those with CRC and controls Methods The systematic review searched through two databases of Medline and Cochrane up to 24th June 2017. The search strategy focused on Population, Intervention, Comparison, and Outcomes (PICO). We searched the role of trace elements in cancer and focusing on case-control studies in CRC to obtain an insight into the differences in trace element concentrations between those with and without cancer. Results The serum concentrations of Ca, Cu, Mg, Mn, Se, Si, and Zn were lower in CRC patients but for Co and S the levels were higher in CRC patients. The concentrations of Cd, Cr, Cu, Mg, Mn, Pb, and Zn were increased in patients with metastasis, but not in Se. As for colon tissue specimens, inconsistent levels were reported between studies, notably in Cu, Se, and Zn. No changes were reported for B and Ca levels. Most of the trace elements in the tissue specimens showed higher concentrations of Cr, Fe, K, Mg, P, Rb, S, and Si compared to Br. Conclusion With the growing interest to understand the link between trace elements in carcinogenesis and the possible interactions, multi assessment analysis of a larger cohort of samples is necessary.
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2018AbstractRecent researchon herbal field reportsvarious ailmentsassociated with free radicals. The risk of ailments because of oxidative stress increasesdue toundesirable way of life, exposure of natural and synthetic chemicals, cigarette smoking, medications, stress and so on. Cancer prevention agents are the substances which can search free radicals and help diminish the frequency of oxidative pressure induced harm. The main sources of antioxidants are vitamins, fruits, minerals, plants and vegetables. The functionsof antioxidants areto neutralize the effect of reactive oxygen species(ROS)and preventvarious diseases such as cancer, diabetes and cardiovascular diseases. The presence of antioxidants can be evaluated by various methods but the cheapest and easiest available methods are 1, 1-diphenyl-2-picrylhydrazyl (DPPH), total antioxidants capacity (TAC), total phenolic contents (TPC), reducing power (RP) and ferric reducing antioxidant potential (FRAP) methods. Thisreviewgenerally discussesthe information related to the antioxidantsand their role in changing the free radicals into neutral or less reactive species. It also discusses therole of antioxidant enrich sources in decreasing the risk of different human diseases.
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Background Breast cancer is the most common serious disease around the world. The trace elements have a vital role in the metabolism and chemotherapy may change the level of metal ions. Due to the ambiguity of the existence in this regard, the study examined the trace element serum levels in women with breast cancer before and after chemotherapy . Methods Sixty patients were studied undergoing specialist. First sampling was taken before chemotherapy (after 4 weeks of surgery) and second sampling was taken after the completion of 3 courses of chemotherapy, approximately 9 weeks after the first chemotherapy. The patients took Adriamycin 60mg/m² Cytoxan 600mg/m². Serum zinc and iron levels were measured using standard spectrophotometric method. Measurement of serum copper was done by atomic absorption spectroscopy. Results Serum zinc and iron levels in women after chemotherapy significantly decreased (p<0.001), however, the serum level of copper increased but was not significant (P=0.676). Conclusions Our findings demonstrate significant decrease in zinc and iron levels in breast cancer patients after 3 courses of Adriamycin and Cytoxan chemotherapy. Prescribing zinc supplements can be useful after chemotherapy.
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Despite significant improvements in the technical aspects of cancer diagnosis and management, it is still a leading cause of mortality worldwide. Although, the development of a variety of therapeutic strategies with effective mechanisms of action is increasing, the advanced understanding of molecular mechanisms of cancer initiation and progression is still the important consequence. Reactive oxygen species (ROS) with great concern due to the ability to modulate cell survival and cell death signaling pathways are could be considered to design the effective anti-cancer strategies. Several anti-cancer agents used for the treatment of various cancers regulates ROSs generation which subsequently modulate the pro-apoptotic molecules, expression of various transcription factors including Sp1, AP1, NF-kβ, and other pro-oncogenic genes that are engaged in cancer cell proliferation, survival and metastasis. Concentration dependent ROS has distinct role in different cancer processes like in apoptosis, cancer survival, autophagy, angiogenesis, metastasis, and inflammation. Radiation and potent agents used in chemotherapy are working on the phenomenon of ROS generation that inhibit cancer process. With the intense understanding of ROS’s role in the particular cancer process which is inevitable in cancer, may be used in health care to improve patient’s survival rate. The current review presents all the proposed molecular interactions of ROS with their known cellular targets in cancer cell.
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In recent years spectral histopathology (SHP) is established as label free method, to identify cancer within tissue. Here, this approach is extended. It is not only used to identify tumour tissue with a sensitivity of 94 % and a specificity of 100 %, but in addition the tumour grading is determined. Grading is a measure how much the tumour cells differ from the healthy cells. The grading refers to G1 (well differentiated) over G2 (moderately differentiated) to G3 (poorly differentiated) and in rare cases to G4 (anaplastic). The grading is prognostic and is needed for the therapeutic decision of the clinician. The presented results showed a nice agreement between the annotation by the SHP and by the pathologists. A correlation matrix is presented. The presented results show, that SHP provide prognostic values in colon cancer, which are obtained label free and automated. It might become an important automated diagnostic tool at the bedside in precision medicine.