









































Pa
ge

 
1



Pa
ge

 
26

American Journal of  Medical 
Science and Innovation (AJMSI) 

Cancer Genetic Markers Among School Children in Relation to 
Urogenital Schistosomiasis

Chinweike-Umeh S.N.1, Ekwunife C.A.1*, Onwuachusi G.L1

Volume 2 Issue 1, Year 2023
https://journals.e-palli.com/home/index.php/ajmsi

Article Information ABSTRACT

Received: February 08, 2023

Accepted: February 26, 2023

Published: March 10, 2023

Chronic infection with urogenital schistosomiasis can lead to severe complications such 
as bladder cancer. Hence, this study determined the presence of  Cancer Genetic Markers 
among School Children in relation to Urogenital Schistosomiasis. All 36 S. haematobium 
positive cases from an earlier study and randomly selected 156 negative samples were used. 
Immunogens tested for, included glyceraldehyde-3-phosphate dehydrogenase (GAPDH) 
and fibroblast growth factor receptor (FGFR3). Mean optical density (OD) was 0.73 and 
0.79 for GAPDH and FGFR3 respectively. A total of  21 (10.94%) participants, 16 females 
and 5 males were positive for GAPDH marker. Fifty (26.04%) participants were positive 
for FGFR3 via ELISA cutoff. Mean OD for S. haematobium positive individuals tested for 
GAPDH was 0.938, minimum value was 0.119 while maximum value was 4.507. For FGFR3 
mean OD was 0.896, Maximum 2.882 and minimum 0.28, while females showed higher 
GAPDH OD. More females than males who were positive for S. haematobium were also 
positive for GAPDH (11.1%) and FGFR3 (25%). FGFR3 and GAPDH marker prevalence 
for Individuals Positive for S. haematobium is 25% and 16.7% respectively. The age group 
11-15 years were the only group positive for GAPDH. There was a slight positive correlation 
between age and FGFR3 and age and GAPDH. The presence of  these markers is an indica-
tor that the children in the selected communities maybe at risk of  developing bladder cancer 
in the future if  the disease is not properly managed and controlled.

Keywords
Bladder Cancer, Genetic 
Markers, Urogenital, 
Schistosoma Haematobium 

1  Department of  Parasitology and Entomology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria
* Corresponding author’s e-mail: ca.ekwunife@unizik.edu.ng

INTRODUCTION
Schistosomes are parasitic trematodes that cause the 
disease schistosomiasis; they are found in subtropical and 
tropical regions of  the world including Nigeria (Ekwunife 
et al., 2004; Ndukwe et al., 2019). Anambra state, Nigeria, 
offer numerous favourable habitats for aquatic snails 
that serve as intermediate hosts to Schistosoma species 
(Ekwunife et al., 2004). Children have been identified to 
harbour the greatest number of  worms leading to reduced 
growth, impaired memory and cognition and reduced 
school attendance (Crompton and Nesheim, 2002; Miguel 
and Kremer, 2004; Bundy et al., 2013). Also, cases of  
chronic infection with urogenital schistosomiasis can lead 
to adverse health outcomes including the development 
of  urogenital cancer. (Ishida and Hsieh, 2018). There are 
certain genetic factors that could also play important role 
in the pathology of  infection with schistosomes including 
the possibility of  the development of  urogenital cancer 
as a result of  granuloma formation (Barosum, 2021). The 
general activity in an individual is controlled by the genetic 
expression of  that individual Therefore information on 
the roles played by some genetic markers in relation to age 
of  individuals predisposed to urogenital schistosomiasis 
will give vital information on the immune protective 
response to the parasite among group of  people that are 
at risk to the development of  severe disease pathology. 
Therefore, this study aimed to determined the presence 
of  Cancer Genetic Markers among School Children in 
relation to Urogenital Schistosomiasis in Anambra North 
Senatorial District, Nigeria

LITERATURE REVIEW
Cancer is a disease of  importance because it is a genetic 
disorder that can come about as a results genetic or 
epigenetic alterations in the somatic cells and is associated 
with abnormal cell growth, it could be invasive or non-
invasive (Soria et al., 2019; Zhang et al., 2015). Cancer has 
been identified to be caused by a lot of  factors including 
but not limited to tobacco smoking, infections like HIV, 
hepatitis b, Epstein-Barretc, poor diet, obesity, excessive 
consumption of  alcohol, exposure to ionizing radiation, 
and gases, bladder inflammation due to microbial and 
parasitic infections, as well as some adverse side-effects 
of  medications (Saini et al., 2020). There are different 
forms of  cancer of  which bladder cancer is inclusive.
Bladder cancer is a disease that can arise from various 
factors including infection with Schistosoma haematobium 
which has significant diagnostic, therapeutic and prognostic 
challenges (Kamat et al., 2013) cases of  which squamous 
cell cancers of  the urinary bladder were identified to be 
proportionately more common in populations with a 
high prevalence of  S. haematobium infection and a high 
proportion of  urinary bladder cancers (IARC, 2012). The 
estimated incidence of  urinary bladder cancer has been 
related to the proportion of  cancerous urinary bladder 
specimens which contains S. haematobium eggs or egg 
remnants (IARC, 2012). Also, the sex ratio of  urinary 
bladder cancer cases show some variation although it 
corresponded to the relative involvement of  men and 
women in agricultural work which has been identified as 
a risk factor for S. haematobium infection (IARC, 2012).

https://journals.e-palli.com/home/index.php/ajmsi


Pa
ge

 
27

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 2(1) 26-31, 2023

Adult worms in Schistosoma haematobium infection are 
seen to reside in the urinary system where they lay eggs 
that cause disease pathology. Studies reported in the 
International Agency for Research on Cancer (IARC) 
and other studies (Badawi et al., 1995; Mostafa et al., 
1999; Mayer and Fried, 2007; Ekwunife et al., 2009) have 
supported an association between the occurrence of  
urinary bladder cancer and S. haematobium infection. 
Studies have shown that: the estimated incidence of  
urinary bladder cancer was higher in areas with a high 
prevalence of  S. haematobium infection than in areas with 
a low prevalence (IARC, 2012). 
Another study on the incidence of  different histological 
types of  bladder cancer in various racial groups living 
within the same geographic area of  Kwazulu-Natal, 
South Africa, reported similar results: squamous cell 
carcinoma occurred in 53% of  the African patients (who 
have a much higher risk of  exposure and infestation 
to S. haematobium due to socioeconomic, cultural and 
educational factors), and in 2% of  the Caucasian patients 
(Groeneveld et al. 1996). Also, Groeneveld et al. (1996) 
reported that eggs of  S. haematobium were seen in 
microscopic sections of  the bladder tumour in 85% of  
the patients with squamous cell carcinoma, and in 10% 
of  the patients with transitional cell carcinoma with the 
mean age at presentation of  African patients was at least 
20 years younger than that of  Caucasian patients.
Adult Schistosoma haematobium worms do not multiply in 
the host, but rather produce offspring that must exit 
the host to continue the parasite life cycle (Klion and 
Nutman, 2002). Helminth species such as Schistosoma 
haematobium have developed complex and redundant 
mechanisms which help them to maintain a chronic 
infection despite immune recognition by the host. 
These parasite are able to attain the chronic infection by 
adoption of  certain strategies which include residing in 
anatomical locations that are relatively free to immune 
attack, molecular mimicry, shedding of  antigenic surface 
proteins, and down- regulation of  the host immune 
response to helminth antigens, thus, producing a state of  
parasite-specific immune tolerance (Brooks et al., 2010).
When an individual gets infected with a parasite or 
any foreign material, the immune system activates the 
humoral and cell mediated immune response (Thomas 
and Harn, 2004; Hokke and Yazdanbakhsh, 2005; Van 
Die and Cummings, 2006; Hokke et al., 2007; Mickum 
et al., 2014), this immune response  can also be found in 
infection with Schistosomes.
Schistosomes are parasites that might not be cleared 
through the process of  phagocytosis by host 
immune responses; therefore, in most cases the host 
immune system responds through inflammation and 
hypersensitivity. Immunoglobulin G (IgG), Eosinophils 
and immunoglobulin E (IgE) are activated to initiate 
inflammatory response in the site where the parasite is 
found.  Infection with Schistosomes has been shown 
to elicit various immune responses such as the induced 
release of  IL- 6, TNF, and IL1-B from monocytes 

(TeVelde et al., 1990), inhibition of  Th17-development 
(Park et al., 2005) and trigger the alternative activation 
of  macrophages with the help of  IL-13  (Gea-Sorlí and 
Closa, 2009). Also, there is the suggestion that 70 % of  
bladder cancers involve a specific mutation in a particular 
gene called the telomerase reverse transcriptase (TERT) 
gene (Zhang and Zhang, 2015). 
The TERT gene is involved in DNA protection, cellular 
aging processes, and cancer. There could be genetic 
mutations in some chromosomal genes, such as FGFR3, 
RB1, HRAS, TP53, TSC1, and others which may play 
certain roles in the formation of  tumors in the urinary 
bladder (Zhang and Zhang, 2015). These genes play an 
important role in the regulation of  gene mutations on 
p53 suppressor gene as was shown in a study which 
evaluated 18 different bladder tumors of  which 11 (61 %) 
had genetic mutations of  p53 gene (Zhang and Zhang, 
2015). The p53 marker has also been associated with the 
most aggressive T1G3 cancers (Soria et al., 2019). HRAS 
is a proto-oncogene and has potential to cause cancer in 
several organs including the bladder. The TSC1 c. 1907 
1908 del (E636fs) mutation in bladder cancer suggests that 
the location of  the mutation is Exon 15 with frequency 
of  TSC1 mutation of  11.7 %. The BAP1 mutations have 
shown that it contributes to BRCA pathway alterations in 
bladder cancer.  The discoveries of  more gene mutations 
and new biomarkers and polymerase chain reaction 
bioassays for gene mutations in bladder cancer need 
further research (Zhang and Zhang, 2015).
The regulation of  the immune response in human 
schistosome infection determines the pathogenic 
response of  the host. Also, an individual’s genetic make-
up is the template on which every of  the organism’s profile 
is written including the individual’s response to diseases 
such as schistosomiasis. Chronic Schistosoma infections are 
usually seen to be established through the modulation of  
the host immune system (Waknine-Grinberg et al., 2010). 
One of  the complications of  urogenital shistosomiasis is 
the formation of  granuloma on the bladder walls, which 
is the main lesion found in schistosomiasis (Ekwunife 
et al., 2009) and is also a predisposing factor to the 
development of  bladder cancer (Ishida and Hsieh, 2018). 
This bladder cancer is the worldwide 9th most common 
cancer (Siegel et al., 2015). Other pathologic effects due 
to S. haematobium include: irregularity of  bladder wall, 
thickening of  the bladder wall, massing of  bladder wall, 
dilated kidney and bladder wall lesions (Ekwunife et al., 
2009). 
In non-invasive tumors, mutations had been found in the 
fibroblasts growth factor receptor 3 (FGFR3) where the 
presence of  the FGFR3 mutation in urine is observed 
for low-grade tumors and are proposed to be associated 
with concomitant or future recurrence (Frantzi et al., 
2012; Critelli et al., 2016). FGFR3 is a genetic marker that 
has been implicated in bladder cancer where some cases 
of  multiple myeloma are seen to express both mutation 
and over-expression of  FGFR3 (Akanksha and Sandhya, 
2019). 

https://journals.e-palli.com/home/index.php/ajmsi


Pa
ge

 
28

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 2(1) 26-31, 2023

Furthermore, there are also studies that has shown that 
there could be increased glyceraldehyde-3-phosphate 
dehydrogenase (GAPDH) levels in many human cancer 
types which has been correlated with possible reduction 
in survival (Altenberg and Greulich, 2004; Guo et al., 
2013).  There had also been report of  deregulation of  
GAPDH in bladder cancer cases (Colell et al., 2009; 
Guo et al., 2013). GAPDH has been implicated to play 
certain roles in apoptosis (Colell et al., 2009) and there 
are suggestion that GAPDH participates in tumor 
progression and could serve as a new therapeutic target 
(Zhang et al., 2015).

MATERIALS AND METHODS 
Ethical Approval: Ethical approval was obtained from 
ethics board of  Nnamdi Azikiwe University Teaching 
Hospital (NAUTH) (NAUTH/CS/66/VOL.13/VER 
III/10/2020/07).
Study Site and Sample Collection: A cross-sectional study 
was earlier carried out in Anambra North Senatorial 
district of  Anambra state for presence of  urogenital 
schistosomiasis (the manuscript on the prevalence 
is presently under review in the Nigerian Journal of  
Parasitology). Anambra north senatorial district is 
made up of  7 local government (LGA) areas which are: 
Anambra East LGA, Anambra west LGA, Ayamelum 
LGA, Ogbaru LGA, Onitsha North LGA, Onitsha 
South LGA and Oyi LGA (MICTU/UNIZIK, 2019). 
Three LGAs were randomly selected.  Informed consent 
from community heads, head teachers and parents were 
obtained before sample collection.  Blood samples (2mls) 
were collected in EDTA bottles for further immunological 
studies. 
A subset of  the general study population was used for 
serology. Two plates of  96 wells was used for the assay. 
The blood samples collected in the EDTA bottles were 
spurned at 3000 revolution per minute for five minutes. 
The plasma was separated from the EDTA container 
into cryogenic vials. The separated plasma was stored 
in cryogenic vials for serology. Serology was done using 
Enzyme Linked Immunosorbent Assay (ELISA). This 
assay was done for both positive and negative samples. 
Immunogens tested for, included glyceraldehyde-3-
phosphate dehydrogenase (GAPDH) and fibroblast 
growth factor receptor (FGFR3). Age range of  individuals 
tested was 6-18 years.  
The Human FGFR3 ELISA Kit and the Anti-GAPDH 
monoclonal Antibody by MyBiosource.com was used 
for this study. The assay procedures were carried out 
following manufacturer’s instructions. Procedure for 
the coating of  plate for the FGFR3 and Anti-GAPDH 
monoclonal Antibody was done following the protocol 
by Thermo Fisher Scientific Inc. (2010). Optical density 
(OD) of  plate was read at 450nm using an ELISA plate 
reader. Wash buffer was prepared using 0.05% tween 20 
and Phosphate buffer saline (PBS). The markers, HRP 

conjugated anti-Rabbit antigen, blocking buffer, Substrate 
and Stop solution were all provided by the manufacturer. 
Data was entered and cleaned in Microsoft excel. Data 
was analyzed using Microsoft Excel and IBM SPSS 20 
software. McNemar’s test and Inter rater reliability tests 
were tested for all ELISA tests. The Fisher exact tests 
and chi-square were used to compare S. haematobium 
infection rates between age and sex. The Spearman’s and 
Pearson correlation coefficient was used to determine 
relationships.

RESULTS AND DISCUSSION
In the said study, a total of  396 children were sampled 
and urine microscopy done for Schistosoma haematobium 
detection. From this, 36 children were positive for 
schistosomiasis. All 36 S. haematobium positive consisting 
of  26 females and 10 males and randomly selected 156 
negative samples were used for the study. The study 
subset included a total of  192 samples, 108 females and 
84 males. Absorbance cutoff  points were determined as 
1.0 and 1.1 for GAPDH and FGFR3 respectively (Figure 
1, Figure 2). Mean optical density was 0.73 and 0.79 for 
GAPDH and FGFR3 respectively. The result from the 
S. haematobium 36 positive cases showed a Mean OD 
for GAPDH as 0.938, minimum value was 0.119 while 
maximum value was 4.507.  For FGFR3 mean OD was 
0.896, Maximum 2.882 and minimum 0.28, while females 
showed higher GAPDH OD (Table 1). 
This study identified that there are some school children 
that are positive for the cancer genetic markers GAPDH 
and FGFR3 in the study area. Also, in the case of  
individuals that are positive for S. haematobium eggs, it 
was also noted that some of  the participants are positive 
for the cancer genetic markers. More positivity rate was 
noted for FGFR3 than GAPDH. A study on S. mansoni 
has sown that there is an indication that the expression 
of  the glycolytic enzyme GAPDH is as a result of  the 
parasite activity (Pirovich et al., 2020). GAPDH has been 
implicated as an immune marker that is essential for cancer 
cells by influencing cancer cell fate and may be a critical 
regulator of  cancer cell functions and hence a marker of  
cancer cell progression and prognosis (Zhang et al., 2015). 
FGFR3 has also been implicated in the development of  
different forms of  cancer and could also serve as cancer 
prognostic marker (Akanksha and Sandhya, 2019).
This basically implies that among this study group, 
there is a risk of  possible progression of  bladder cancer 
development if  infection with urogenital schistosomiais 
is not well managed. This should be an issue of  public 
health importance since this implies potential risk of  
bladder cancer development because, the positivity for 
these markers identifies that there is a potential risk of  
them developing bladder cancer in the future because, 
these markers could serve as cancer prognostic markers 
(Akanksha and Sandhya, 2019; Zhang et al., 2015).
A total of  21 (10.94%) participants were positive for 

https://journals.e-palli.com/home/index.php/ajmsi


Pa
ge

 
29

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 2(1) 26-31, 2023

Figure 1: Scatter plot of  GAPDH ELISA detection results.

Figure 2: Scatter plot of  FGFR3 ELISA detection results.

Table 1: OD and Prevalence of  GAPDH and FGFR3 by Sex
GAPDH FGFR3
Female Male Female Male

Mean OD 0.876 0.557 0.822 0.733
Max OD 4.448 4.507 2.26 2.882
Min OD 0.14 0.119 0.248 0.225
No. Negative (%) 92 (85.2) 79 (94) 82 (75.9) 60 (71.4)
No. Positive (%) 16 (14.8) 5 (6.0) 26 (24.1) 24 (28.6)
Total 108 84 108 84
P>0.05

GAPDH while 50 (26.04%) participants were positive 
for FGFR3 via ELISA cutoff  (Table 2). Age range of  
individuals tested was 6-18 years. There was a slight positive 
correlation between age and GAPDH though this was not 
statistically significant (r= 0.27, p>0.005). There was also 
a slight positive correlation between age and FGFR3 (r= 
0.27, p>0.005). S. haematobium positive individuals in the 
age group 11-15 years were the only group positive for 
GAPDH while for FGFR3 positivity was noticed across 
all age groups (Table 3). This study was also able to show 
that there was a weak positive correlation between age 
and GAPDH and age and FGFR3 for the general assayed 
population though this was not statistically significant. 

Individuals from the assayed samples in the age group 11-
15 years had a slightly higher GAPDH OD though those 
in the age group 6-10 years had more positive individuals 
for the assayed marker. On the other hand, individuals 
assayed for FGFR3 had more positive cases for those in 
age group 11-15 years. Furthermore, in individuals that 
are positive for S. haematobium there was no relationship 
between age and the presence of  the markers. Though it 
was noted that six (6) individuals in the age group 11-15 
years who were positive for S. haematobium eggs were also 
positive for GAPDH while for FGFR3 there were positive 
cases across the different age group represented in the 
study. This may imply that the risk of  the development of  

https://journals.e-palli.com/home/index.php/ajmsi


Pa
ge

 
30

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 2(1) 26-31, 2023

urogenital cancer increases with age as it had been noted 
that age is the greatest single risk factor for developing 
urogenital cancer (Shariat et al., 2019). This could also 
be an indication that the expression of  these markers 
is more represented with an increase in years of  school 

children in the sampled communities. A study by Ahmad 
et al (2018) identified that older age patients tend to show 
increased frequency of  FGFR3 mutations. 
Mean FGFR3 and GAPDH OD was higher in females 
than males. GAPDH mean OD for females was 0.876 

Table 2: Prevalence of  GAPDH and FGFR3 in various age group
GAPDH FGFR3

Age (Years) Total Positive Prevalence (%) Positive Prevalence (%)
0-5 0 0 0 0 0
6-10 72 12 16.67 16 22.22
11-15 83 6 7.32 24 29.27
16-20 38 3 7.89 10 26.32
Total 192 21 10.94 50 26.04
P>0.05

Table 3: GAPDH and FGFR3 Prevalence for Individuals Positive for S. haematobium in various age group
GAPDH FGFR3

Age (Years) Total Positive Prevalence (%) Positive Prevalence (%)
0-5 0 0 0 0 0.00
6-10 9 0 0 5 13.89
11-15 18 6 16.67 5 13.89
16-20 9 0 0 3 8.33
Total 36 6 16.67 13 36.11

while male was 0.557. FGFR3 mean OD for females 
was 0.866 and males was 0.733. Prevalence of  GAPDH 
showed that 16 (14.8%) of  the 108 females were positive 
while 5 (6.0%) of  84 males were positive for the marker. 
Also, 26 (24.1%) females and 24 (28.6%) males were 
positive for FGFR3 (Table 1). More females positive for 
S. haematobium were also positive for GAPDH (11.1%) and 
FGFR3 (25%) (Table 4). FGFR3 and GAPDH marker 
prevalence for Individuals Positive for S. haematobium 
is 25% and 16.7% respectively. In this study, female 
participants showed higher mean GAPDH and FGFR3 
OD than male participants. Also, for those positive for 

S. haematobium there were more females positive for the 
marker than males. This occurrence may be attributed to 
the fact that they are the most exposed group since they 
carry out day to day activities in potentially infected S. 
haematobium water bodies and this could make them more 
likely to present with the markers. This is in line with other 
studies on FGFR3 gene mutation studies that identified 
that female patients tend to show increased frequency 
of  FGFR3 mutations (Beukers et al., 2017; Ahmad et al., 
2018). In contrast, another study had reported that the 
presentation of  this marker is more common in male 
than female (Akanksha and Sandhya, 2019). However, 

Table 4: GAPDH and FGFR3 Prevalence for Individuals Positive for S. haematobium in various age group
GAPDH FGFR3
Overall Female Male Overall Female Male

Average OD 0.956 1.155 0.694 0.896 1.018 0.782
Maximum OD 4.507 4.027 4.507 2.882 2.882 2.26
Minimum OD 0.119 0.229 0.119 0.28 0.364 0.28
Prevalence (%) 6(16.7) 4(11.1) 2(5.6) 13(36.1) 9(25) 4(11.1)

this study noted that there is no relationship between sex 
and the presence of  the markers in participants that are 
positive for S. haematobium. Moreover, the International 
Agency for Research on Cancer has stated that bladder 
cancer could be associated with the profession of  an 
individual and is more related to Agricultural farmer 
(IARC, 2012) because of  their contact with infected 
water. 

CONCLUSIONS 
The study has produced evidence showing that there are 
children that are positive for the cancer genetic markers 
FGFR3 and GAPDH with more females being positive 
for the markers. The presence of  these markers are an 
indicator that children in the selected communities 
maybe at risk of  developing bladder cancer in the future 

https://journals.e-palli.com/home/index.php/ajmsi


Pa
ge

 
31

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 2(1) 26-31, 2023

if  the disease is not properly managed and controlled. 
Also, there is need for more studies on these identified 
immune markers which may serve as prognostic markers 
for schistosomiasis progression or urogenital cancer 
development in at risk population.
This study has potential limitations. This study does not 
have age representation for children 0-5 years. Though, 
this has no direct impact on the result of  the findings 
for the other age groups represented. However, further 
research can be done to include the age group 0-5years 
to ascertain the representation of  the cancer genetic 
markers of  the group. Also, determining the marker 
concentration using a standard curve will help elucidate 
more on the relationship between concentration and the 
different categories assayed in this study.

REFERENCES
Ahmad, F., Mahal, V., Verma, G., Bhatia, S., and Das, 

B.R. (2018). Molecular Investigation of  FGFR3 Gene 
Mutation and Its Correlation with Clinicopathological 
Findings in Indian Bladder Cancer Patients. Cancer 
Reports, 1(3), e1130.

Akanksha, M., and Sandhya, S. (2019). Role of  FGFR3 in 
Urothelial Carcinoma. Iranian Journal of  Pathology, 14, 
148–155.

Altenberg, B., and Greulich, K.O. (2004). Genes of  
glycolysis are ubiquitously overexpressed in 24 cancer 
classes. Genomics, 84, 1014-1020.

Barosum, R.S. (2021). The Kidney in Schistosomiasis: 
Chapter 56. Retrieved on May 01, 2021. https://
abdominalkey.com/the-kidney-in-schistosomiasis/ 

Beukers, W., van der Keur, K.A., Kandimalla, 
R.,Vergouwe, Y., Steyerberg, E.W., Boormans, J.L., 
Jensen, J.B.Lorente, J.A., Real, F.X., Segersten, U., 
Orntoft, T.F., Malats, N., Malmström, P-U., Dyrskjot 
L. and Zwarthoff, E.C. (2017). FGFR3, TERT and 
OTX1 as a Urinary Biomarker Combination for 
Surveillance of  Patients With Bladder Cancer in 
A Large Prospective Multicenter Study. Journal of  
Urology, 197(6),1410- 1418. 

Brooks, G.F., Carroll, K.C., Butel, J.S., Morse, S.A., 
Mietzner. T.A., (2010). Jawetz, Melnick & Adelberg’s 
Medical Microbiology (25th edition). McGraw Hill, 
New York.

Bundy, D.A.P., Walson, J.L. and Watkins, K.L. (2013). 
Worms, Wisdom, and Wealth: Why Deworming can 
make Economic Sense. Trends in Parasitolology, 29, 142-
148.

Cheesbrough M. (2009). District Laboratory Practice 
in Tropical Countries, part 1. 2nd edn Cambridge: 
Cambridge University Press.

Colell A., Green D.R. and Ricci J.E. (2009). Novel roles 
for GAPDH in cell death and carcinogenesis. Cell 
Death Differ, 16, 1573-1581.

Critelli R, Fasanelli F, Oderda M, Polidoro S, Assumma 
MB, Viberti C, Preto M, Gontero P, Cucchiarale 
G, Lurkin I, Zwarthoff  EC, Vineis P, Sacerdote C, 
Matullo G, and Naccarati A. (2016). Detection of  

multiple mutations in urinary exfoliated cells from 
male bladder cancer patients at diagnosis and during 
follow-up. Oncotarget, 7(41), 67435–67448.

Crompton, D.W.T. and Nesheim, M.C. (2002). Nutritional 
Impact of  Intestinal Helminthiasis during the Human 
Life Cycle. Annual Review of  Nutrition, 22, 35-59.

Ekwunife, C.A., Okafor, F.C. and Nwaorgu, O.C. 
(2009). Ultrasonographic screening of  urinary  
Schistosomiasis infected patients in Agulu community, 
Anambra state, southeast Nigeria. International Archives 
of  Medicine, 2, 34.

Ekwunife, C.A., Ukaga, C.N. and Okafor, F. (2004). 
Urinary Schistosomiasis in Anambra State, Nigeria. 
Nigerian Journal of  Parasitology, 25(1), 127-131.

Frantzi, M., Makridakis, M. and Vlahou, A. (2012). 
Biomarkers for bladder cancer aggressiveness. Current 
Opinion Urology, 22(5), 390–396.

Gea-Sorlí, S. and Closa, D. (2009). In vitro, but not 
in vivo, reversibility of  peritoneal macrophages 
activation during experimental acute pancreatitis. 
BMC Immunology, 10, 42.

Groeneveld, A.E., Marszalek, W.W. and Heyns, C.F. 
(1996). Bladder cancer in various population groups 
in the greater Durban area of  KwaZulu-Natal, South 
Africa. British Journal of  Urology, 78, 205–208.

Guo C., Liu S. and Sun M-Z (2013). Novel Insight into 
the Role of  GAPDH Playing in Tumor. Clinical and 
Translational Oncology, 15(3), 167-72.

Hokke, C.H. and Yazdanbakhsh,M., (2005).Schistosome 
Glycans and Innate Immunity. Parasite Immunology, 27, 
257–264.

IARC (2012). Biological agents. Volume 100 B. A review 
of  human carcinogens. IARC  monographs on the 
evaluation of  carcinogenic risks to humans/World 
Health Organization. International Agency for Research on 
Cancer, 100, 1–441.

Ishida, K. and Hsieh, M.H. (2018). Understanding 
urogenital Schistosomiasis-Related Bladder Cancer: 
An Update. 

Kamat, A.M., Hegarty, P.K., Gee, J.R., Clark, P.E., Svatek, 
R.S., Hegarty, N., Shariat, S.F., Xylinas, E., Schmitz-
Dräger, B.J., Lotan, Y., Jenkins, L.C., Droller, M., van 
Rhijn, B.W. and Karakiewicz, P.I. (2013) ICUD–EAU 
international consultation on bladder cancer 2012: 
screening,  diagnosis, and molecular markers. Eur 
Urol, 63, 4–15.

Klion, A.D. and Nutman, T.B. (2002). Immunity to 
Parasitic Worms. Encyclopedia of  Life Science: 
MacMillian Publishers Limited.

Mickum, M.L., Prasanphanich, N.S., Heimburg-
Molinaro, J., Leon, K.E. and Cummings, R.D. (2014). 
Deciphering the Glycogenome of  Schistosomes. 
Frontiers in Genetics, 5(262), 1-15.

MICTU/UNIZIK (2019). Centre for Community and 
Rural Development: Anambra North Senatorial 
District. Retrived on April 14, 2019. https://ccrd.
unizik.edu.ng/anambra-senetorial-districts/anambra-
north-senetorial-district/

https://journals.e-palli.com/home/index.php/ajmsi


Pa
ge

 
32

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 2(1) 26-31, 2023

Miguel, E. and Kremer, M. (2004). Worms: Identifying 
Impacts on Education and Health in the Presence of  
Treatment  Externalities. Econometrica, 72, 159-217.

Ndukwe, Y.E., Obiezue, R.N.N., Aguzie, I.O.N., Anunobi, 
J.T. and Okafor, F.C. (2019). Mapping of  Urinary 
Schistosomiasis in Anambra State, Nigeria. Annals of  
Global Health, 85(1), 1–10.

Park, H., Li, Z., Yang, X.O., Chang, S.H., Nurieva, R., 
Wang, Y.H., Wang, Y., Hood, L., Zhu, Z., Tian, Q. 
and Dong, C. (2005). A distinct lineage of  CD4 T 
cells regulates tissue inflammation by producing 
interleukin 17. Nature Immunology, 6, 1133-1141.

Pirovich, D.B., Da’dara, A.A. and Skelly, P.J. (2020). 
Schistosoma mansoni glyceraldehyde-3-phosphate 
dehydrogenase enhances formation of  the blood-
clot lysis protein plasmin. Biology Open, 9. https://doi.
org/10.1242/bio.050385

Saini, A., Kumar, M., Bhatt, S., Saini, V. and Malik, A. 
(2020). Cancer Causes and Treatment. International 
Journal of  Pharmaceutical Science and Research 11(7), 3121-
3134.

Shariat S.F., Sfakianos J.P., Droller M.J.,Karakiewicz 
P.I.,Meryn S., and Bochner B.H. (2019). The effect of  
age and  gender on bladder cancer: a critical review of  
the literature. BJU International, 105(3), 300–308.

Siegel, R.L., Miller, K.D. and Jemal, A. (2015). Cancer 
Statistics. CA: A Cancer Journal for Clinicians. 
American Cancer Society, 65(1), 5-29.

Soria, F., Krabbe, L-M., Todenhöfer, T., Dobruch, J., 
Mitra, A.P., Inman, B.A., Gust, K.M., Lotan, Y. and 

Shariat, S.F. (2019). Molecular markers in bladder 
cancer. World Journal of  Urology, 37, 31–40.

teVelde, A.A., Huijbens, R.J., Heije, K., de Vries, J.E. 
and Figdor, C.G. (1990). Interleukin-4 (IL-4) inhibits 
secretion of  IL-1 beta, tumor necrosis factor alpha, 
and IL-6 by human monocytes. Blood, 76, 1392-1397.

Thermo Fisher Scientific Inc. (2010). ELISA technical 
guide and protocols. http://tools.thermofisher.com/
content/sfs/brochures/TR0065-ELISA-guide.pdf. 

Thomas, P.G. and Harn, D.A. (2004). Immune Biasingby 
Helminth Glycans. Cellular Microbiology, 6, 13–22.

Van Die, I. and Cummings, R.D. (2006). Glycans 
Modulate Immune Responses in Helminth Infections 
and Allergy.  Chemical Immunology and Allergy, 90, 91–
112.

Waknine-Grinberg, J.H., Gold, D., Ohayon, A., Flescher, 
E., Heyfets, A., Doenhoff, M.J., Schramm, G., Haas, 
H. and Golenser, J. (2010). Schistosoma mansoni 
infection reduces the incidence of  murine cerebral 
malaria. Malaria Journal, 9, 5.

Zhang X and Zhang Y (2015). Bladder Cancer and 
Genetic Mutations. Cell Biochemistry and Biophysis 73, 
65–69.  https://doi.org/10.1007/s12013-015-0574-z

Zhang, J-Y., Zhang, F., Hong, C-Q., Giuliano, A.E., 
Cui, X-J., Zhou, G-J., Zhang, G-J. and Cui, Y-K. 
(2015). Critical protein GAPDH and its regulatory 
mechanisms in cancer cells. Cancer Biology and Medicine, 
12, 10-22.

https://journals.e-palli.com/home/index.php/ajmsi

