












































 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e1                                              Cancer Health Disparities 

RESEARCH 

Cortisol and Health-related Quality of Life 
as Prognostic Indicators for Prostate 
Cancer Risk in West African Black Men in 
Nigeria, Cameroon and the USA: The 
CaPTC Cohort Study 
Mohammed Faruk*1,2, Folakemi T. Odedina1,3,4, Sani Ibrahim1,5, Abdulmumini Hassan Rafindadi1,2, Ahmed 
Adamu1,6, Danladi Amodu Ameh1,5, Sirajo Mohammed Aminu1,7, Abdullahi Adamu1,8, Ahmad Bello1,6, Ernie 
Kaninjing1,9, John Idoko1,10, Aishatu Maude Suleiman1,7, Solomon O. Rotimi1,11, , Getachew A. Dagne1,12, Nissa 
Askins1,3,4, Clayton C Yates1,13, Emeka J. Iweala1,11, Yawale Iliyasu1,2, Iya Eze Bassey1,14, R. Renee Reams1,15, 
Abdullahi Mohammad1,2, Mohammed Sani Shehu1,2, Abdullahi Jubril Randawa,1,16 Hussaini Yusuf Maitama1,6, 
Dauda  M. Maigatari1,6, Abdulkadir Lawal Rafinadadi1,17, Ahmad Bello Kumo1,18, Haruna A Nggada1,19 
Rebecca Gali1,20, Hassan  M. Dogo1,21, Ademola Popoola,1,22 Serah Adewumi1,22, Ruth Agaba1,11, Kimberly 
Meza1,3,4, Nkegoum Blaise1,23, Paul Jibrin1,24, Rakiya Saidu,1,25,26 Haruna Mohammad Muktar1,7, Ahmad Mai1,6, 
Titilola Akinremi1,27, Sunday Ene-Ojo Atawodi1,5, Saad Aliyu Ahmed1,2, Aliyu Muhammad1,5, Kasimu Umar 
Adoke1,2, Ahmad Tijjani Lawal1,6, Jamilu Ya’u,1,28 Ahmed Muhammed1,6, Muhammad Sa’idu Tanko1,29 

Omolara Fatiregun1,30, Aliyu A Babadoko1,7 Shehu Akuyam1,31, Yusuf Rasheed1,31, Mubarak Labaran Liman1,32, 
Abidemi E Omonisi1,33, Anthonia Sowunmi1,34, Jigo Dangude Yaro1,2, Catherine Adebukola Oladoyinbo1,35, 
Faoziyat Adenike Sulaiman,1,22 Ogo Chidiebere Ndukwe,1,27 Abdussamad Abdulrahaman,1,36 Olubanke O. 
Ogunlana,1,11, Ayo A Salako1,37, Frank Chinegwundoh1,38, Wole Kukoyi,1,39 Esther Isaiah1,39 Adenike Onibokum  
1,40, Ibrahim Suleiman1,41, Motolani E Ogunsanya1,42, Fredrick Ugwumba1,43 , Okezie Mbadiwe1,43 , Kayode 
Adeniji,1,22, Akinwumi Oluwole Komolafe1,44, Suleiman Alege Kuranga,1,22 Iheanyi Okpala1,45 

1 Prostate Cancer Transatlantic Consortium (CaPTC); 2 Department of Pathology, College of Health 
Sciences, Faculty of Basic Clinical Sciences, Ahmadu Bello University, Zaria 810001, Nigeria; 3Department of 
Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Orlando, Florida 
32827, USA; 4Minority Cancer Research and Training (MiCaRT) Center, University of Florida, Orlando, 
Florida, USA; 5Department of Biochemistry, Faculty of life Sciences, Ahmadu Bello University, Zaria Nigeria; 
6Department of Surgery, College of Health Sciences, Faculty of Clinical Sciences, Ahmadu Bello University, 
Zaria Nigeria; 7Department of Haematology and Blood Transfusion, College of Health Sciences, Faculty of 
Basic Clinical Sciences, Ahmadu Bello University, Zaria, Nigeria; 8Department of Radiology and 
Radiotherapy, College of Health Sciences, Faculty of Clinical Sciences, Ahmadu Bello University, Zaria, 
Nigeria, 9School of Health and Human Performance, Georgia College and State University, Milledgeville, 
Georgia 31061 USA 10Department of Pathology, Ahmadu Bello University Teaching Hospital Shika Zaria, 
Nigeria; 11Department of Biochemistry, Covenant University, Ota, Ogun State, Nigeria; 12Department of 
Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, Florida USA; 
13Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee Alabama 36088, 
USA; 14Department of Medical Laboratory Science, Faculty of Allied Medical Health Sciences, College of 



 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e2                                              Cancer Health Disparities 

RESEARCH 

Medical Sciences, University of Calabar, Calabar, Nigeria.1,15College of Pharmacy and Pharmaceutical 
Sciences, Florida A&M University, Tallahassee, Florida USA; 16Department of Obstetrics and Gynaecology, 
College of Health Sciences, Faculty of Basic Clinical Sciences, Ahmadu Bello University, Zaria, Nigeria; 
17Department of Ophthalmology, College of Health Sciences, Faculty of Basic Clinical Sciences, Ahmadu 
Bello University, Zaria, Nigeria; 18Department of Medicine, College of Health Sciences, Faculty of Basic 
Clinical Sciences, Ahmadu Bello University, Zaria, Nigeria; 19Department of Pathology, College of Medical 
sciences, University of Maiduguri, Maiduguri, Nigeria; 20Department of Medical laboratory Science, College 
of Medical sciences, University of Maiduguri, Maiduguri, Nigeria; 21Department of Surgery, College of 
Medical sciences, University of Maiduguri, Maiduguri, Nigeria; 22Faculty of Basic Clinical Sciences, College 
of Health Sciences, University of Ilorin, Ilorin, Nigeria; 23University Hospital Center, Yaounde, Cameroon; 
24Department of Pathology, National Hospital, Abuja, Nigeria; 25Department of Obstetrics and 
Gynaecology, Faculty of Medicine, University of Ilorin, Ilorin, Nigeria; 26Department of Obstetrics and 
Gynaecology, University of Cape Town, South Africa; 27Federal Medical Center, Abeokuta, Nigeria; 
28Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Ahmadu Bello 
University, Zaria Nigeria; 29Veterinary Teaching Hospital, Ahmadu Bello University Zaria, Nigeria   
30Department of Radiotherapy and Oncology, Lagos State University Teaching Hospital, Lagos, Nigeria; 
31Department of Chemical Pathology, College of Health Sciences, Faculty of Basic Clinical Sciences, 
Ahmadu Bello University, Zaria, Nigeria; 32Department of Science Laboratory Technology, Nuhu Bamalli 
Polytechnic, Zaria, Nigeria; 33Department of Anatomic Pathology, Faculty of Basic Clinical Sciences, Ekiti 
State University, Ado-Ekiti, Nigeria; 34Department of Radiotherapy, Lagos University Teaching Hospital, 
Lagos, Nigeria; 35Department of Nutrition and Dietetics Federal University of Agriculture, Abeokuta, 
Nigeria; 36Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical 
Sciences, Ahmadu Bello University, Zaria Nigeria; 37Department of Surgery, Obafemi Awolowo University, 
Ile-Ife, Nigeria; 38Barts Health NHS Trust/ School of Health Sciences, City University London, UK; 39Ace 
Medicare Clinics Limited Ota, Nigeria; 40Department of Nursing Sciences, University of Ibadan, Ibadan 
Nigeria; 41Department of Physiology, Ahmadu Bello University, Zaria, Nigeria; 42College of Pharmacy, 
Health Science Center, University of Oklahoma Health Science Center, Oklahoma City, OK 73117, USA; 
43Department of Surgery, University of Nigeria, Nsuka, Nigeria; 44Department of Pathology, Obafemi 
Awolowo University, Ile-Ife, Nigeria; 45Institute of Human Genomics and Infectious Diseases, University of 
Nigeria, Nsukka, Nigeria 

*Corresponding Author: Mohammed Faruk, E-mail: fmohammed@abu.edu.ng 

 

 

 

 

 

 

mailto:fmohammed@abu.edu.ng


 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e3                                              Cancer Health Disparities 

RESEARCH 

 

 

ABSTRACT 
Poor understanding of the clinicopathological features of prostate cancer (CaP) in Black men (BM) is 
one of the major challenges implicated in the management and prevention of the disease. The 
development of CaP involves an accumulation of multiple oncogenic events with associated increase in 
prostate specific antigen (PSA) and stress related hormones such as Cortisol.  This research aims to 
examine the role of Cortisol and health-related quality of life (HRQoL) in CaP development. Data was 
collected as part of a large CaPTC Familial CaP Cohort Study.  The HRQoL indicators were measured 
and salivary Cortisol levels evaluated by enzyme immunoassay. CaP tissue expression patterns of 
cortisol and Annexin V were also studied by immunohistochemistry. The HRQoL indicators showed a 
significant difference between participants with and without physical activity (P = 0.025), stress (P = 
0.008) and self-care (P = 0.005). There was significant increase in salivary cortisol levels in the CaP 
patients compared to CaP-free participants (P = 0.003). The salivary cortisol level for the CaP patients 
ranged from 1.029 µg/dL to 0.037 µg/dL while the range for the CaP-free participants was from 0.139 
µg/dL to 0.026 µg/dL. In addition, we found increased expression of the cortisol protein in CaP patients 
with Gleason score 8 compared to those with lower scores and the CaP tissues showed overexpression 
of Annexin V protein. Salivary and tissue cortisol levels with an accompanying Annexin V expression may 
serve as important biomarkers for CaP diagnosis and prognosis in West African Black men. 

KEYWORDS: Prostate Cancer, African Black Men, Nigerian Men, Cameroonian Men, Cortisol, Health 
Related Quality of Life 

Citation:  Faruk et al (2019) Cortisol and Health-related Quality of Life as Prognostic Indicators for Prostate 
Cancer Risk in West African Black Men in Nigeria, Cameroon and the USA: The CaPTC Cohort Study. 
Cancer Health Disparities 4: e1-17. doi:10.9777/chd.2019.1009. 
 
 



 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e4                                              Cancer Health Disparities 

RESEARCH 

INTRODUCTION 

Prostate cancer (CaP) is a significant public health 
challenge that has disproportionately 
overburdened Black men of African ancestry with 
increased prevalence, poor prognosis and heavy 
mortality rates (Odedina et al., 2009 (a); Bray et al., 
2013). A number of studies have documented 
significant CaP burden among Nigerian and 
Cameroonian Black men in West Africa and the 
diaspora (Odedina et al., 2009 (b); Kumar et al., 
2009; Akinremi et al., 2011; Odedina et al., 2011(a); 
Odedina et al., 2011 (b); Enow Orock et al., 2012; 
Ferlay et al., 2015; Kaninjing et al., 2017; Odedina et 
al., 2017). In African Americans, the incidence and 
mortality rates of CaP are disproportionately 
higher than in Caucasians, and the prognosis 
worse, due largely to genetic factors (Odedina et 
al., 2009 (b); American Cancer Society, 2013). 
Personal factors (such as lack of awareness), 
provider factors (such as shortage of human 
resources) and healthcare systems factors (such as 
limited access to appropriate treatment) contribute 
to the late CaP presentation with metastatic 
disease as the first presenting features at diagnosis 
in Black men of African ancestry (Farré and Kibera, 
2018). It is pertinent to note that available 
diagnostic and prognostic tools for CaP which 
includes prostate specific antigen (PSA) lack 
specificity and sensitivity. This makes it difficult to 
distinguish between aggressive and nonaggressive 
state of the disease for proper stratification, further 
evaluation and therapeutic intervention (Farran et 
al., 2018). To explore the distinct biological and 
environmental etiology of CaP, the Prostate 
Cancer Transatlantic Consortium (CaPTC - 
https://epi.grants.cancer.gov/captc/), a US 
National Institutes of Health (NIH)/ National 
Cancer Institute (NCI) – Epidemiology and 
Genomics Research Program (EGRP) approved 

consortium, utilizes multilevel, collaborative, 
transdisciplinary, translational, and global team 
science research approach to study Black men 
globally. Specifically, CaPTC investigators address 
the complexity of CaP taking into consideration 
the ethnic heterogeneity and geographical 
classifications of Black men with African ancestry. 
This approach is pertinent to understanding the 
etiology of African-associated CaP risk and 
utilizing the diverse West African population will 
be of immense benefit. 

The initial state of CaP and its progression involves 
an accumulation of multiple oncogenic events 
resulting in gene amplification, which is associated 
with increased levels of androgens and prostate-
specific antigen (PSA). The PSA has been reported 
to be higher in Black men compared to 
Caucasians, however, this has been associated with 
complications and controversies (Visakorpi et al., 
1995; Moul et al.., 1996; US Preventive Services 
Task Force Recommendation Statement, 2018). 
The complications with increase in PSA level are 
aggravated by several abnormal mutations that 
make CaP cells more aggressive via the stress and 
cortisol axis mechanisms and an increase in the 
amino acid content within the cancer 
microenvironment (Gaddipati et al., 1994; Zhao et 
al., 2000; Wang et al., 2013; Tee, 2013; Huang et 
al., 2018). In addition, amino acids via anabolic 
pathways generate nucleotide and membrane 
biomolecule precursors for aggressive CaP cells 
(Andrew et al., 2013). Perhaps, this explains why 
leucine may serve as a source of fuel for 
aggressive prostate cancer cells. However, it has 
not been unequivocally demonstrated that leucine 
is secreted mostly by Cortisol overexpression.  

The Cortisol, an important glucocorticoid 
hormone, is synthesized in the body by adrenal 

https://epi.grants.cancer.gov/captc/


 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e5                                              Cancer Health Disparities 

RESEARCH 

cortex via adrenocorticotropin stimulation. 
Therefore, cortisol fluctuation as a result of stress 
has been linked to allostatic load-associated 
diseases including immune suppression 
(Kirschbaum and Hellhammer, 1999). Only about 
5% of Cortisol is unbound and freely circulate to 
the tissues including salivary gland for biological 
activity, whereas the remaining 95% is bound to 
several components of the blood including 
corticosteroid-binding globulin (Ekins, 1990; 
Walker et al., 1978). Thus, saliva provides a simple 
and non-invasive means of assessing unbound 
cortisol level because blood cortisol levels may be 
affected by the corticosteroid-binding globulin 
activity (Walker et al., 1978). 

Health-related quality of life (HRQoL) has also 
been reported to be associated with PSA status in 
men with CaP (Gidron et al., 2011). Since a 
deficiency in Cortisol secretion results to quiescent 
immune system and overexpression of Cortisol 
contribute to suppression of immune responses 
and possible tumorigenesis (Munck and Naray-
Fejes-Toth, 1995; Coussens and Werb, 2002), our 
study focused on the expression pattern of 
Cortisol in CaP tissue cells, taking into 
considerations the Gleason score by 
immunohistochemistry. The ability of Cortisol to 
regulate immunological and inflammatory 
processes prompted us to explore the expression 
pattern of Annexin V, an intracellular protein with 
affinity to phosphatidylserine, which is expressed 
on the surface of physiologically stressed cells and 
functions in inhibition of cancer angiogenesis 
(Blankenberg, 2009).   

In line with our long-term goal of addressing the 
burden of CaP in West African men, the primary 
objective of this study was to examine the role of 
Cortisol and HRQoL in the development of CaP 

among Nigerian and Cameroonian men living in 
Nigeria, Cameroon and United States. Findings 
from this study show significant differences in 
HRQoL, salivary cortisol level and tissue Cortisol 
expression pattern in the CaP patients compared 
to CaP-free participants. These findings may have 
a significant impact on CaP risk and prognosis, 
and may contribute to the understanding of the 
genetic, environmental and behavioral etiological 
factors associated with the disease in Black men.  

METHODS 

Study Participants and Recruitment 
The participants recruited for this pilot study were 
Nigerian and Cameroonian Black men within the 
age bracket of 35 to 70 years and residing in 
Nigeria, the Republic of Cameroon and the United 
States of America (US) - Participants were 
recruited as part of the large-scale CaPTC study 
focused on studying a familial cohort of West 
African men in multiple countries. The CaPTC 
study (which is ongoing) is using the heterogeneity 
of the study participants, including geographical 
locations, to explore the genetic, environmental 
and behavioral etiological factors associated with 
CaP. The study inclusion criteria were: (1) West 
African men regardless of the history of CaP 
diagnosis; (2) men between the age of 35 and 70 
years; and (3) men who consented to complete 
the study survey. Participants were recruited from 
multiple settings using a flyer, including at clinics 
and diverse community settings such as social 
organizations, churches, mosques, health events 
and also business facilities.  

Study Variables and Measures 
The study variables were: (1) health-related quality 
of life indicators including exercise, stress, ability to 
self-care and perceived emotional health status,-; 



 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e6                                              Cancer Health Disparities 

RESEARCH 

(2) personal history of CaP,-; and (3) demographic 
information, including age, religion, ethnicity, 
education, income, employment, country of 
residence, and previous history of cancer. These 
variables were assessed using the standardized 
Global Prostate Cancer Measure for Black men 
that was developed by CaPTC and the African 
Caribbean Cancer Consortium (AC3). 

Data Collection  
Ethical approval was obtained at each study site 
prior to data collection. The ethics approval 
include implementing informed consent process 
for each participant. Following informed consent 
approval by participants, the key study personnel 
in charge of data collection administered the 
survey and collected saliva drool using a saliva kit. 
The salivary samples were collected from 8am to 
12 noon. Participants were provided a monetary 
incentive or a T-shirt for the time taken to 
participate in the study.  

Statistical Considerations and Data Analyses 
The study data entry and management was 
conducted using the Research Electronic Data 
Capture (REDCap) software. Subsequently, data 
were exported into the PC-SAS analytical software 
for data analysis. Frequency analysis of the 
variables was conducted to confirm responses are 
appropriately entered and errors corrected. The 
internal consistency of the study scales was 
calculated to establish the reliability of the scales. 
The study variables were evaluated using 
descriptive statistics of means procedure for 
continuous variables and frequency analyses for 
categorical variables. Microsoft Excel (Microsoft 
Office Professional Plus 2013; Microsoft Corp., 
Redmond, WA, USA) was used to produce the 
charts. Subsequently t-test statistical analysis was 
used to determine the differences in cortisol levels 

and expression using the SPSS software, version 
20.0 (IBM Corp., Armonk, NY, USA). A P -value of 
<0.05 was considered statistically significant.  

Salivary Cortisol Analysis by Enzyme-linked 
Immunosorbent Assay  
The salivary cortisol was quantified using an 
enzyme-linked immunosorbent assay (ELISA) kit 
(Salimetric Inc, College Park, PA) as per 
manufacturer’s procedure. All ELISA experiments 
were performed in duplicate analysis.  

Tissue Cortisol Analysis by Immunohistochemistry  
Immunohistochemistry (IHC) was performed on 5-
μm CaP formalin fixed paraffin embedded (FFPE)  
tissue and non-malignant prostatic FFPE tissues for 
cortisol and Annexin V protein expression using 
Anti-Cortisol (ABIN3208586) and Anti-Annexin V 
(BIN4964891) antibodies (antibodies-online 
Aachen, Germany). Briefly, the slides containing 
tissue sections were baked for 1 hour, then  
deparaffinized with 100% xylene at room 
temperature for 1 minute, and hydrated in a 
graded alcohol stages consisting of 30-second 
dips each in 100% and 95% ethyl alcohol diluted in 
water (total volume is 5 mL) at room temperature, 
and finally hydrated in water. Sections were 
incubated in 3% hydrogen peroxidase in water at 
room temperature for 10 minutes to block 
endogenous peroxidase activity. The slides were 
then washed, blocked and incubated at room 
temperature for 30 minutes. The slides were 
incubated with the Anti-cortisol antibody and in 5 
µg/ml dilutions and with HRP-linked secondary 
antibody in blocking buffer. The same protocol 
was used for Anti-Annexin V (BIN4964891) 
antibody staining using 2.5 µg/ml. The nuclei of 
the cells were counterstained with haematoxylin 
(blue). The expression level was categorized as low 
and high based on a combined score of intensity 



 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e7                                              Cancer Health Disparities 

RESEARCH 

and distribution. The expression was categorised 
base on intensity of the stain (0 = absent; 1 = 
weak; 2 = moderate; 3 = strong) and distribution 
(per cent of tumour positive). 

RESULTS 

A total of 500 Black men of West African descent 
participated in the study. Of the 500 Black men, 
85% are resident in Nigeria, 8% in the USA and 7% 
in the Republic of Cameroon. Demographic 
characteristics of the participants are displayed in 
Table 1. The results revealed that 8% (40) of the 
participants had previous diagnosis of prostate 
cancer whereas 1% (4) had previously been 
diagnosed with other malignancies such as 
colorectal, liver, nasopharyngeal cancers and 
sarcoma. About 82% (401) of the participants were 
non-smokers and 85% (427) were employed. 

Table 1. Demographic Characteristic for the CaPTC 
Cohort Study. 
Characteristics Frequency  Percent 
Demographic characteristics, n = 500 
Country of resident   
Nigeria 428  85.60 
Cameroon 34  6.80 
USA 38  7.60 
Age range of participants recruited 
35-44 216  43.20 
45-54 160  32.00 
55-64 82  16.40 
65 and above 42  8.40 
Personal history of cancer 
Prostate cancer 40 8.00 
Colorectal cancer 2 0.40 
Liver cancer 1 0.20 
Nasopharyngeal  1 0.20 
Sarcoma 1 0.20 
Do not know  455 91.00 
Marital status 
Married or living as married 460 92.00 

Never married or divorced/ 
widowed 

37 7.40 

Non-disclosed 3 0.60 
Smoking status 
At present 20 4.00 
In the past 72 14.40 
Never 329 68.80 
Non-disclosed 79 15.80 
Education 
8 to 11th grade 87 17.4 
High school 108 21.6 
University 294 58.8 
Non-Disclosed  11 2.20 
Employment Status 
Employed  427 85.40 
Not employed 63 12.60 
Non-Disclosed  10 2.00 
Household income 
Less than $25,000 419 83.80 
$25,000 to $49,999  10 2.00 
$50,000 to $74,999 9 1.80 
$75,000 and above 15 3.00 
Non-disclosed  47 9.40 

Participant’s health-related quality of life  
Five relevant factors associated with HRQoL 
indicators were examined in this study: exercise, 
stress, ability to self-care, health status perception 
and the need for specialized equipment towards 
personal daily life support. Results show significant 
differences (P = 0.0353) in participants physical 
activity levels within the last month, with 57% of 
participants reporting up to 30 days active 
exercise, 19% reporting 0 to 9 days of no exercise, 
3% reporting 10 to 19 days of no exercise, and 4% 
reporting 20 to 30 days of no exercise within the 
last month (see Figure 1). There was also 
significance difference (P = 0.0080) across stress 
levels of participants within the last month. Sixty-
four per cent (64%) of participants reported 
absence of emotional stress for 30 days within the 
last month, 13% reported presence of stress for 0 



 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e8                                              Cancer Health Disparities 

RESEARCH 

to 9 days, 3% reported presence of stress for 10 to 
19 days and 3% reported presence of stress for 20 
to 30 days (Figure 1). 

There were significant differences (P = 0.0051) in 
participants’ report on self-care within the last 
month. Sixty-three (63%) indicated that they had 
not been able to carry out self-care for 30 days, 
16% indicated that they had not been able to carry 
out self-care for 0 to 9 days, 2% had not been 
able to carry out self-care for 10 to 19 days and 3% 
had not been able to carry out self-care 20 to 30 
days. 

In general, most of the participants reported good 
healthcare status. Eighty-four per cent of the 
participants indicated that they were in good 

health while 14% reported poor or fair health 
within the last month. Furthermore, 94% of the 
participants reported that they had no need for 
specialized equipment to carryout daily personal 
activities while 4% reported that they needed 
special equipment for daily life activities within the 
last month.  

Table 2 compares HRQoL indicators between 
participants with history of CaP and CaP-free 
participants. The HRQoL indicators show no 
significant difference in exercise (P = 0.1441), stress 
(P = 0.1789), ability to self-care (P = 0.1434), health 
status perception (P = 0.3066), and need for 
specialized equipment (P = 0.3784) between 
patients with history of CaP and CaP-free 
participants.  

 

Figure 1. Summary of Health Related Quality of Life of participants recruited.  

 



 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e9                                              Cancer Health Disparities 

RESEARCH 

 

 

Figure 2. Response of perceived health status of the participants.   

Table 2. Comparison of health-related quality of life for participants with history of prostate cancer and 
prostate cancer-free participants. 
Variable s Participants with CaP 

History N=40 (%) 
Participant without CaP 
History N=460 (%) 

P-value 

Exercise     
30 days Active Exercise 19 (47.5) 289 (64.3) 0.1441 
No Exercise 0-9 days 13 (32.5) 101 (21.9)  
No Exercise 10-19 2 (5.0) 14 (3.0)  
No Exercise 20-30 days 3 (7.5) 13 (2.8)  
No response 3 (7.5)  43 (7.9)  
Stress     
No stress 30 days 22 (55.0) 316 (70.1) 0.1789  
Stress 0-9 days 8 (20.0) 61 (13.3)  
Stress 10-19 days 2 (5.0) 14 (3.1)  
Stress 20-30 days 3 (7.5) 13 (2.8)  
No response 5 (12.5)  56 (10.7)  
Ability to self-care    
Self-care 30 days 25 (62.5) 290 (63.0) 0.1434 
No self-care 0-9 6 (15.0) 74 (16.1)  
No self-care 10-19 3 (7.5) 7 (1.5)  
No self-care 20-30   2 (5.0) 13 (2.8)  
No response 4 (10.0) 76 (16.5)  

0

10

20

30

40

50

60

70

80

90

100

Good –
Excellent 

Health

Poor – Fair 
Health

Unclassified Do not Need
Special

Equipment

Need Special
Equipment

Unclassified

Re
sp

on
se

 o
f t

he
 S

ub
je

ct
s (

%
) 

Perceived Health Status Scale of the Subjects Recruited 



 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e10                                              Cancer Health Disparities 

RESEARCH 

Health status perception    
Good to excellent  20 (50) 390 (84.8) 0.3066 
Poor to fair  17 (42.5) 63 (13.7)  
No response 3 (7.5) 7 (1.5)10  
Need for specialized equipment     
Do not need  24 (60) 436 (94.8) 0.3784 
Need 13 (32.5) 11 (2.4)  
No response 3 (7.5) 13 (2.8)  
 
Salivary cortisol levels of CaP patients and CaP-
free participants  
Results from the salivary cortisol analysis by ELISA 
show significant increase in expression (P =0.003) 
of salivary Cortisol levels (0.18±0.03) in the 
prostate cancer patients (N=10) compared to the 
values (0.08±0.01) from the CaP-free participant 
(N=40) (Figure 3A). The maximum value of the 
salivary Cortisol level among the CaP patients was 
1.029 and the minimum value was 0.037. The 
maximum and minimum values of the salivary 
Cortisol in CaP-free participants were 0.139 and 
0.026 respectively (Figure 3B). 

 

Figure 3A. Salivary Cortisol levels of few of the 
participants recruited. 

 

Figure 3B. Salivary Cortisol levels from a portion of CaP patients and CaP-free participant recruited.  One 
of the CaP participants in position 8 above showed abnormal increase in cortisol even after repeating the 
analysis for accuracy. 

0

0.2

0.4

0.6

0.8

1

1.2

1 2 3 4 5 6 7 8 9 10

Prostate Cancer Patients

Control Subjects

Sa
liv

ar
y 

Co
rt

iso
l L

ev
el

s (
µg

/d
L)

 

Cap patients and CaP-free participants 



 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e11                                              Cancer Health Disparities 

RESEARCH 

Tissue Cortisol and Annexin V expression in CaP 
patients and CaP-free participants 
Result show overexpression of Cortisol protein in 
the CaP cases with Gleason score of 8 compared 
to those with lower Gleason scores. The CaP-free 
tissues show negative expression of the Cortisol 
protein (Figure A).  Figure 4B contains H&E stained 
sections of CaP showing CaP cells and 3 different 
sections stained for IHC with the Anti-Cortisol 

antibody signifying strong expression of the 
cortisol protein. The sections are CaP cases with 
Gleason score of 8 .  Also shown in the IHC result 
is moderate expression of Cortisol protein in the 
CaP cells with lower Gleason score of 6 and below 
(Figure 4C). All but one of the CaP cases stained 
with Anti-Annexin V antibody show increased 
expression of Annexin V protein (Figure 4D). 

 

 



 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e12                                              Cancer Health Disparities 

RESEARCH 

 

Figure 4A. Left: Benign or non-malignant prostate tissue stained with Haematoxylin and Eosin (H&E), and 
Right: Anti-Cortisol antibody stain for showing no cortisol expression in the prostate. Figure 4B: Cortisol 
expression pattern in CaP cells with Gleason score 8. The top left photograph is an H&E stained section of 
CaP tissue showing malignant cells.  The other photographs show sections of CaP cells with Gleason score 
8 stained by immunocytochemistry with Anti-Cortisol antibody; there is strong expression of Cortisol. Fig 
4C: Expression pattern of Cortisol in CaP cells with Gleason Score 6 and below. The IHC result show 
moderate expression of the Cortisol in the cells. 

 

Figure 4D. Expression pattern of Annexin V protein in CaP cells. The stain shows all but one of the CaP 
sections stained with Anti-Annexin V antibody to have increase expression of the protein. 



 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e13                                              Cancer Health Disparities 

RESEARCH 

 

Figure 4E. Show H score depicting pattern of Cortisol expression in normal prostatic lesion and CaP cells. 
The score show 2-fold increase in Cortisol expression in the CaP sections.

DISCUSSION 

The results from this CaPTC pilot study of 500 
West African Balck men within the age bracket of 
35 and 70 years show variation in HRQoL 
indicators such as exercise, stress, and ability to 
self-care, health status perception and the need 
for specialized equipment in carrying out daily life 
activities. The most interesting finding was, 
indicators associated to HRQoL themes appeared 
to have the existence of about 3% of the 
respondents reporting their inability to carry out 
daily exercise, self-care and hence consistent stress 
for 20 to 30 days within period of one month. The 
percentage of the HRQoL indicators increased 
slightly to about 19% for the participants when 
increasing the number of days for physical activity 
by 10 days. Poor health-related quality of life 
parameters which interfere with physical, 
functional, social and emotional states of an 
individual have been associated to worsen disease 
prognosis especially in African American men with 
CaP (Blankenberg 2009; DeSantis et al., 2012). 
Previous studies have showed that Western 
lifestyle, reduced physical activity and high fat diet 

intake are related to CaP risk (Freedland and 
Aronson, 2009; Fradet et al., 2009). Stress and 
psychosocial factors are also associated with the 
onset and prognosis of malignant tumours. A 
recent meta-analysis of 165 studies reports that 
psychosocial factors are predictive of cancer 
prognosis, independent of initial tumor stage and 
other confounders (Chida et al., 2008). Of the 500 
study participants, 40 were patients diagnosed 
with CaP, thus contributing to the percentage of 
the participants with poor health-related quality of 
life in this research.  

Results that compare HRQoL indicators between 
participants with history of CaP and CaP-free 
participants show no significant differences 
between the two groups. The lack of differences in 
the HRQoL indicators between the groups may be 
associated to the small number of CaP participants 
(N=40) as compared to CaP-free participants 
(N=460) recruited in this study. However, since the 
study recruitment is on-going, further effort will lay 
emphasis on recruiting sufficient CaP patients.   

The salivary Cortisol level analysis of 40 
participants without CaP and 10 patients with CaP 

E 



 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e14                                              Cancer Health Disparities 

RESEARCH 

showed a significant increase in the mean average 
Cortisol level from 0.08±0.01 to 0.18±0.03 
respectively. However, one of the patients with 
CaP showed a four-fold increase in salivary 
Cortisol level compared to the highest level in the 
non-CaP participants even after repeating the 
analysis to rule out possible errors. Previous 
studies have shown that Cortisol levels are 
associated with circadian disruption and poor 
health status which in turn contribute to immune 
dysfunction and CaP risk (Touitou 1983; Coussens 
and Werb, 2002; DeSantis et al., 2012; Tai et al., 
2016). Findings from this study further showed 
about 14% of the respondents to have poor health 
status, while 4% needed specialized equipment to 
be able to perform regular daily activities, 
probably for reasons, not unrelated to stress.   

Additionally, the expression patterns of Cortisol 
protein at tissue level were assessed by 
immunohistochemistry to further explore the role 
of the protien in CaP pathogenesis. The results 
obtained show an increase in the expression of the 
Cortisol in CaP cells, which was directly associated 
with increase in Gleason score and hence the 
disease aggressiveness. The luminal cells of the 
glandular epithelium in CaP secrete various 
hormones including androgens (Feldman and 
Feldman, 2001) and perhaps Cortisol for a role in 
cellular proliferation and apoptosis.  Previous 
report shows that stress increases cytokines level 
especially interleukin 6 on the hypothalamic-
pituitary-adrenal axis (Zhou et al., 1993) which may 
result to fluctuation in the body Cortisol level. The 
T877A androgen receptor mutation in the CaP 
microenvironment increases the binding affinity of 
the androgen receptor to Cortisol and its 
metabolite, cortisone, creating a cortisol 
responsive CaP cells leading to androgen 
independent growth and higher tumour grade 

(Zhao et al., 2000). Interestingly, the abnormal 
mutations of the androgen receptor molecule 
results in the ability of cortisol to bind to the 
androgen molecule thereby functioning as a 
“pseudo-androgen”, promoting the increase in 
secretion of PSA and making CaP cells more 
aggressive (Gaddipati et al., 1994; Zhao et al., 
2000). These factors explain the potential source 
and role of cortisol in CaP. CaP cells with 
metastatic features including metastatic castration-
resistant phenotypes have been reported to be 
highly dependent on amino acid uptake through 
the L-amino acid transporters (LATs) for cellular 
growth and proliferation, as well as malignant 
transformation (Wang et al., 2013). The LATs are 
part of ATF4 genes that function in the exchange 
of branch chain amino acids for intracellular amino 
acids (Tee, 2013). Amino acids via anabolic 
pathways have been reported to generate 
nucleotide and membrane biomolecule precursors 
for aggressive CaP cells (Tee, 2013). Perhaps this 
explains why leucine may serve as a source of fuel 
for aggressive prostate cancer cells. The study also 
shows increased tissue expression of annexin V 
protein in the CaP cells. Annexin V have been 
reported to regulate immunological and 
inflammatory processes and commonly expressed 
on the surface of stressed cells for inhibition of 
malignant tumour angiogenesis (DeSantis et al., 
2012). 

Previous findings have shown that abnormal 
increase in stress contributes to increase in 
Cortisol, inflammation and immune dysfunction via 
activation of the hypothalamic-pituitary-adrenal 
axis (Blankenberg, 2009). These underlining 
mechanisms have been proposed to play 
significant role in prostate cancer pathology and 
poor prognosis (Touitou et al., 1983; Gidron et al., 
2011; Coussens and Werb 2002; DeSantis et al., 



 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e15                                              Cancer Health Disparities 

RESEARCH 

2012; Tai et al., 2016). The limitation of our pilot 
study includes the small sample size of participants 
with CaP compared to CaP-free participants. 
Additional research parameters which include but 
not limited to inflammatory markers are necessary 
to increase our understanding of the role of 
Cortisol in the development and prognosis of CaP 
in Black African men. Further in-depth studies that 
take into consideration all the necessary 
parameters are required.   

CONCLUSION  

In conclusion, this study to a large extent has 
demonstrated associations of salivary Cortisol 
level, tissue cortisol expression activity and HRQoL 
of life in West African Black men in Nigeria, 
Cameroon and the USA with or without CaP. The 
study show that salivary and tissue Cortisol levels 
with an accompanying Annexin V expression may 
serve as important biomarkers for prostate cancer 
diagnosis and prognosis in West African Black 
men. The findings further suggest the possibility 
that tissue and salivary Cortisol in combination 
with indicators of HRQoL may mediate prostate 
cancer risk in West African Balck men.   

Acknowledgements 
We acknowledge the support of Mrs. Nike 
Obafemi who assisted with data collection and our 
participants who took the time to participate in this 
study. In addition, Ms. Kimberly Meza is 
acknowledged for providing editorial review for 
the manuscript. 

Funding Support  
Funding support for this project was provided by 
the Prostate Cancer Transatlantic Consortium 
(CaPTC).  

Conflict of interest 

The authors declare that no competing or conflict of 
interests exist. The funders had no role in study 
design, writing of the manuscript, or decision to 
publish. 

Authors’ contributions 
Conception and design: MF, FTO, SA, AA, SMA, 
Abdullahi Adamu, AB, JI, AMS, EK, CCY, RRR,  

Development of methodology: MF, FTO, RRR, CY, 
FC, SO 

Acquisition of data: MF, NA, SA,AMS, RA, KM 

Analysis and interpretation of data: MF, GAD, NA  

Writing, review, and/or revision of the manuscript: 
MF, FTO, SI, AHR, AA, DAA, SMA, Abdullahi Adamu, 
AB, EK, JI, AMS, SOR,  GAD, NA, CCY, EJI, YI, IEB, 
RRR, AM, MSS, AJR, HYM, DMM, ALR, ABK, HAN, 
RG, HMD, AP, SA, RA, KM, NB, PJ, RS, HMM, Ahmad 
Mai, TA, SEA, SAA, Aliyu Muhammad, KUA, ATL, JY, 
Ahmad Muhammad, MST, OT , AAB, Shehu Akuya 
YR, MLL, AEO, AS, JDY, CAO, FAS, OCN, AA, OOO, 
AAS, FC, WK, EI, AO, IS, MEO, FU, OM, KA, AOK, 
SAK, IO. 

Administrative, technical, or material support: NA, 
SA, RA, KM 

Study supervision: MF 

 

REFERENCES 
Akinremi, T.O., Ogo, C.N., and Olutunde, A.O. (2011).  Review 

of prostate cancer research in Nigeria. Infectious Agent 
Cancer 2011: 6; (Suppl 2):S8.  

American Cancer Society: Cancer Facts & Figures for African 
Americans 2013–2014 Atlanta, American Cancer Society; 
20013 https://www.cancer.org/content/dam/cancer-
org/research/cancer-facts-and-statistics/cancer-facts-
and-figures-for-african-americans/cancer-facts-and-
figures-for-african-americans-2013-2014.pdf  

https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-facts-and-figures-for-african-americans/cancer-facts-and-figures-for-african-americans-2013-2014.pdf
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-facts-and-figures-for-african-americans/cancer-facts-and-figures-for-african-americans-2013-2014.pdf
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-facts-and-figures-for-african-americans/cancer-facts-and-figures-for-african-americans-2013-2014.pdf
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-facts-and-figures-for-african-americans/cancer-facts-and-figures-for-african-americans-2013-2014.pdf


 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e16                                              Cancer Health Disparities 

RESEARCH 

Bray, F., Ren, J.S., Masuyer, E., and Ferlay, J. (2013). Global 
estimates of cancer prevalence for 27 sites in the adult 
population in 2008. International Journal of Cancer 132, 
1133–1145.   

Blankenberg, F.G. (2009). Imaging the Molecular Signatures of 
Apoptosis and Injury with Radiolabeled Annexin V. 
Proceeding of the American Thoracic Society 6, 469–476.  

Chida, Y., Hamer, M., Wardle, J., and Steptoe, A. (2008). Do 
stress-related psychosocial factors contribute to cancer 
incidence and survival? Nature Clinical Practice Oncology 
5, 466-475.  

Coussens, L. M. and Werb, Z. (2002). Inflammation and 
cancer. Nature 420, 860–867.  

DeSantis, A.S., DiezRoux, A.V., Hajat, A., Aiello, A.E., Golden, 
S.H., Jenny, N.S., Seeman, T.E., and Shea, S. (2012). 
Associations of salivary cortisol levels with inflammatory 
markers: The multi-ethnic study of atherosclerosis. 
Psychoneuroendocrinology 37, 1009–1018.  

Ekins, R. (1990). Measurement of free hormones in blood. 
Endocrine Reviews 11, 5-46.  

Enow Orock, G.E, Ndom, P., and Doh, A.S. (2012). Current 
Cancer Incidence and Trends in Yaounde, Cameroon. 
Oncology, Gastroenterology and Hepatology Reports 1, 
58-63.   

Farran, B., Dyson, G., Craig, D., Dombkowski, A., Beebe-
Dimmer, J.L., Powell, I.J., Podgorski, I., Heilbrun L., Bolton, 
S., and Bock, C.H. (2018). A study of circulating 
microRNAs identifies a new potential biomarker panel to 
distinguish aggressive prostate cancer. Carcinogenesis 
39, 556–561  

Farré, X., and Kibera J. (2018). The untapped potential of 
digital pathology in prostate cancer diagnosis and 
medical education in sub-Saharan Africa. African Journal 
of Urology 24, 54-55  

Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., 
Rebelo, M., Parkin, D.M,, Forman, D., and Bray, F. (2015). 
Cancer incidence and mortality worldwide: sources, 
methods and major patterns in GLOBOCAN 2012. 
International Journal of Cancer  136, E359-E386  

Fradet, V., Cheng, I., Casey, G., and Witte, J.S. (2009). Dietary 
omega-3 fatty acids, cyclooxygenase-2 genetic variation, 
and aggressive prostate cancer risk. Clinical Cancer 
Research 15, 2559-2566.  

Freedland, S.J., and Aronson, W.J. (2009). Dietary intervention 
strategies to modulate prostate cancer risk and 
prognosis. Current Opinion in Urology 19, 263-267.  

Gaddipati, J.P., McLeod, D.G., Heidenberg, H.B., Sesterhenn, 
I.A., Finger, M.J., Moul, J.W., Srivastava, S. (1994). 
Frequent detection of codon 877 mutation in the 
androgen receptor gene in advanced prostate cancers. 
Cancer Research 54, 2861–2866.  

Gidron, Y,. Fabre, B., Grosman, H., Nolazco, C., Mesch, V., 
Mazza, O., and Berg, G. (2011). Life events, cortisol and 
levels of prostate specific antigen: a story of synergism. 
Psychoneuroendocrinology 36, 874-880.  

Huang, Y., Jiang, X., Liang, X., and Jiang G. (2018). Molecular 
and cellular mechanisms of castration resistant prostate 
cancer. Oncology Letters. 15, 6063-6076 

Kaninjing, E., Rahman, S., Close, F., Pierre, R., Dutton, M., 
Lamango, N. and Onokpise, O. (2017).  Prostate cancer 
screening knowledge, attitudes, and beliefs among men 
in Bamenda, Cameroon. International Journal of Public 
Health and Epidemiology 6, 339 – 349.  

Kirschbaum, C., and Hellhammer, D.H. (1999). Noise and stress 
- salivary cortisol as a non-invasive measure of allostatic 
load. Noise Health 1, 57-65.   

Kumar, N.B., Yu, D., Akinremi, T.O., and Odedina, F.T. (2009).  
Comparing Dietary and other Lifestyle Factors among 
immigrant Nigerian Men living in the US and Indigenous 
Men from Nigeria: Potential Implications for Prostate 
Cancer Risk Reduction. Journal of Immigrant and Minority 
Health. Journal of Immigrant and Minority Health 11, 391-
399.    

Moul, J.W., Sesterhenn, I.A., Connelly, R.R., Douglas, T., 
Srivastava, S., Mostofi, F.K., and McLeod, D.G. (1995). 
Prostate-specific antigen values at the time of prostate 
cancer diagnosis in African-American men. Journal of the 
American Medical Association 274, 1277-1281.   

Munck, A, Naray-Fejes-Toth, A. Glucocorticoid action In 
Endocrinology 3rd edn (ed. DeGroot, L.) 1642–1654 (W.B. 
Saunders Co,1995). 

Odedina, FT., Yu, D., Akinremi, T.O., Reams, R.R., Freedman, 
M.L., and Kumar, N. (2009). (a). Prostate Cancer 
Cognitive-Behavioral Factors in a West African 
Population. Journal of Immigrant and Minority Health 11, 
258-267.  

Odedina, F.T., Akinremi, T.O., Chinegwundoh, F., Roberts, R., 
Yu, D., Reams, R.R., Freedman, M.L., Rivers, B., Green, 
L.B., and Kumar N. (2009). (b). Prostate cancer disparities 
in Black men of African descent: a comparative literature 
review of prostate cancer burden among Black men in 
the United States, Caribbean, United Kingdom, and West 
Africa. Infectious Agents and Cancer 2009, 4 (Suppl 1):S2.  

Odedina, F.T., Dagne, G., Pressey, S., Odedina, O., Emanuel, 
F., Scrivens, J., Reams, R.R, Adams, A., and LaRose-Pierre, 
M. (2011). (a). Prostate cancer health and cultural beliefs 
of black men: The Florida Prostate Cancer Disparity 
Project. Infectious Agents and Cancer 2011, 6(Suppl 
2):S10.   

Odedina, F.T., Dagne, G., LaRose-Pierre, M., Emanuel, F., 
Scrivens, J., Adams, A., Pressey, S., Odedina, O. (2011). (b). 
Within-group differences between native-born and 
foreign-born Black men on prostate cancer risk reduction 



 
 
 
 
 

 
www.companyofscientists.com/index.php/chd                   e17                                              Cancer Health Disparities 

RESEARCH 

and early detection practices. Journal of Immigrant and 
Minority Health 13, 996-1004.  

Odedina, F.T., Young, M.E., Pereira, D., Williams, C., Nguyen, 
J., and Dagne G. (2017). Point of Prostate Cancer 
Diagnosis (PPCD) Experiences of Black Men: The Florida 
CaPCaS Study. Journal of Community and Supportive 
Oncology 15, 10-19.  

Tai, S.Y., Huang, S.P., Bao, B.Y., and Wu, M. (2016.) Urinary 
melatonin-sulfate/cortisol ratio and the presence of 
prostate cancer: A case-control study. Scientific Reports 
6, 29606.  

Tee, A.R. (2013). Metastatic Castration-Resistant Prostate 
Cancer Hungers for Leucine. Journal of the National 
Cancer Institute 105, 1427–1428.  

Touitou ,Y., Sulon, J., Bogdan, A., Reinberg, A., Sodoyez, J.C., 
and Demey-Ponsart, E. (1983). Adrenocortical hormones, 
ageing and mental condition: Seasonal and circadian 
rhythms of plasma 18-hydroxy-11-deoxycorticosterone, 
total and free cortisol and urinary corticosteroids. Journal 
of Endocrinology, 96, 53–64.  

US Preventive Services Task Force Recommendation 
Statement. (2018). Screening for Prostate Cancer. Journal 
of the American Medical Association 319, 1901-1913.  

Visakorpi, T., Hyytinen, E., Koivisto, P., Tanner, M., Keinänen, 
R., Palmberg, C., Palotie, A., Tammela, T., Isola, J., and 
Kallioniemi, O.P. (1995). In vivo amplification of the 
androgen receptor gene and progression of human 
prostate cancer. Nature Genetics 9, 401–406.  

Walker, R.F., Riad-Fahmy, D. and Read, G.F. (1978). Adrenal 
status assessed by direct radioimmunoassay of cortisol in 
whole saliva or parotid saliva. Clinical Chemistry 24, 1460-
1463.  

Wang, Q., Tiffen, J., Bailey. C.G., Lehman. M.L., Ritchie. W., 
Fazli. L., Metierre. C., Feng, Y.J., Li, E., Gleave, M., 
Buchanan, G., Nelson, C.C., Rasko, J.E., and Holst, J. 
(2013). Targeting amino acid transport in metastatic 
castration-resistant prostate cancer: effects on cell cyle, 
cell growth, and tumor development. Journal of the 
National Cancer Institute 105, 1463-1473.   

Zhao, X.Y., Malloy, P.J., Krishnan, A.V., Swami, S., Navone, 
N.M., Peehl, D.M., and Feldman D. (2000). 
Glucocorticoids can promote androgen-independent 
growth of prostate cancer cells through a mutated 
androgen receptor. Nature Medicine 6, 703–706  

Zhou, D., Kusnecov, A.W., Shurin, M.R., DePaoli, M., ans Rabin, 
B.S. (1993). Exposure to physical and psychological 
stressors elevates plasma interleukin 6: relationship to the 
activation of hypotha-lamic-pituitary-adrenal axis. 
Endocrinology 133, 2523-30. 

 
 
 

 
 


