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RESEARCH

Androgen metabolism genes in prostate 
cancer health disparities 
 
Wei Liu1,2, Runhua Liu2,3, Lizhong Wang2,3* 
1Provincial Key Laboratory on Molecular and Chemical Genetic,  The Second Hospital of Jilin University, 
Changchun 130041, PR China  
2Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294 
3Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294 
 
*Corresponding author e-mail: lwang12@uab.edu 
 

ABSTRACT 
For men in the United States, prostate cancer is common, and newly diagnosed cases of 

prostate cancer outnumber those of all other cancer types. For prostate cancer, there are racial 
disparities between Caucasian Americans and African Americans. Androgens and androgen metabolism 
may be involved in these disparities as well as in the initiation and progression of prostate cancer. Here, 
we analyzed, in the Cancer Genome Atlas (TCGA) database, the mRNA expression of genes involved in 
androgen metabolism in prostate cancer based on the patient’s race. The results revealed that 
expressions of UGT2B15 and CYP3A5 are higher but that SRD5A2, CYP17A1, HSD3B2, and AKR1C3 are 
lower in African American prostate cancers than in those of Caucasian Americans. These genes may 
relate to the racial disparities associated with prostate cancer. However, the evidence require validation 
and functional analysis. 
 
KEYWORDS: prostate cancer; racial disparity; androgen; metabolism; gene expression 
 
Citation: Liu W. Liu R, Wang L (2017). Androgen metabolism genes in prostate cancer health disparities 
Cancer Health Disparities;1:e1-e6. doi:10.9777/rr.2017.10003

  



 
 
 
 
 

 
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INTRODUCTION 
According to the latest statistics provided by the 
American Cancer Society (ACS), there are 161,360 
incident cases newly diagnosed with prostate 
cancer, accounting for 19% of all new cancer cases 
in 2017 and, for males, leading all other cancers 
(Siegel et al., 2017). The incidence varies with race. 
The rate for African American (AA) men is 
198.4/100,000, higher than 114.8/100,000 for 
Caucasian American (CA) men. Although the racial 
disparities in prostate cancer are related to 
lifestyle, dietary, socioeconomic, and clinical 
factors, genetic factors are also substantial (Chang 
et al., 2014; Cooper and Page, 2014; Plata Bello 
and Concepcion Masip, 2014; Schaid, 2004; Singh 
et al., 2017). For most prostate cancers, which are 
generally androgen-sensitive, androgen 
withdrawal can produce initial regressions (Cooper 
and Page, 2014). Lower levels of intraprostatic 
androgens are associated with a lower incidence 
of prostate cancer (Cooper and Page, 2014). 
Androgen deprivation therapy, a common 
treatment, can block progression of metastatic 
prostate cancer (Welsh and Hentz, 2017; Yang et 
al., 2017; Young et al., 2017). Further, differences in 
androgen metabolism may relate to the racial 
disparities in this disease (Singh et al., 2017). Thus, 
for prostate cancer, androgen metabolism may be 
involved in racial disparities as well as in tumor 
imitation and progression. 
For CA and AA men in the United States, there are 
differences in androgen levels. Serum testosterone 
levels of AA men (aged 31 to 50) are about 15% 
higher than those of CA men (Ellis and Nyborg, 
1992; Singh et al., 2017). In prostate tissues of AA 
men, androgens, androstenedione, and sex 
hormone-binding globulin levels are greater than 
those in tissues of CA men (Singh et al., 2017). 
Likewise, for AA men, expression of the androgen 
receptor (AR) protein is 22% higher in benign 
prostate tissue and 81% higher in prostate cancer 
tissue relative to CA men (Gaston et al., 2003). 
These differences may contribute to racial 
disparities for prostate cancer. Other factors, such 

as age, body mass index, prostate specific antigen, 
and pathologic Gleason grade, may be involved in 
these disparities (Plata Bello and Concepcion 
Masip, 2014; Schaid, 2004). However, whether 
genes involved in androgen metabolism are 
primary factors for these racial disparities is not 
known. Therefore, with the Cancer Genome Atlas 
(TCGA) database, we conducted an expression 
analysis of genes involved in androgen 
metabolism in prostate cancer based on the 
patient’s race. From the findings, we have 
presented a potential mechanism underlying 
androgen metabolism in racial disparities for 
prostate cancer. 

 
RESULTS AND DISCUSSION 
We analyzed the mRNA expression of 20 genes 
involved in androgen metabolism, including 
AKR1C2, AKR1C3, CYP3A4, CYP3A5, CYP7B1, 
CYP11A1, CYP17A1, CYP19A1, HSD3B1, HSD3B2, 
HSD17B3, HSD17B6, HSD17B10, RDH5, RDH16, 
SRD5A1, SRD5A2, SRD5A3, UGT2B7, and UGT2B15, 
by use of a web-portal UALCAN tool 
(Chandrashekar et al., 2017) for analyses of TCGA 
gene expression data in 52 normal prostate 
tissues, 147 CA prostate cancer tissues, and 6 AA 
prostate cancer tissues. For AA tissues, there were 
significantly higher expressions of 5 genes, 
including HSD3B2 (cancer/normal fold change = 
1.11; p = 4.31x10-2), HSD17B3 (fold change = 3.22; p 
= 1.11x10-16), HSD17B10 (fold change = 1.27; p = 
1.79x10-12), SRD5A1 (fold change = 1.27; p = 
4.02x10-5), and SRD5A3 (fold change = 1.14; p = 
2.58x10-3), but significantly lower expressions of 9 
genes, including AKR1C2 (fold change = 0.32; p = 
9.42x10-3), CYP3A5 (fold change = 0.14; p = 
1.32x10-3), CYP11A1 (fold change = 0.21; p = 
3.85x10-8), CYP19A1 (fold change = 0.27; p = 
4.32x10-2), CYP7B1 (fold change = 0.52; p = 
2.20x10-4), HSD17B6 (fold change = 0.59; p = 
6.56x10-4), RDH5 (fold change = 0.50; p = 5.76x10-
5), SRD5A2 (fold change = 0.23; p = 5.73x10-10), 
and UGT2B7 (fold change = 0.00; p = 1.83x10-2). Of 
note, expressions of AKR1C3, CYP3A5, CYP17A1, 



 
 
 
 
 

 
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HSD3B2, SRD5A2, and UGT2B15 showed significant 
differences in prostate cancer tissues between CA 
men and AA men (Figure 1). Expressions of 
CYP3A5 (fold change = 1.38; p = 4.32x10-2) and 
UGT2B15 (fold change = 1.87; p = 4.32x10-2) in AA 
prostate cancers were higher than those for CA 
prostate cancers, but expressions of AKR1C3 (fold 

change = 0.58; p = 4.32x10-2), CYP17A1 (fold 
change = 0.50; p = 4.32x10-2), HSD3B2 (fold 
change = 0.77; p = 4.32x10-2), and SRD5A2 (fold 
change = 0.71; p = 4.32x10-2) were lower in AA 
prostate cancers than in CA prostate cancers 
(Figure 1). 

 

 
 

Figure 1. mRNA expression of genes involved in androgen metabolism in normal prostate tissues and 
prostate cancers based on the race of patients as determined with the TCGA database. CA, Caucasian 
American; AA, African American. 
AKR1C3 is associated with a reduction of 
androstenedione and lower (Mostaghel and 
Nelson, 2008) production of testosterone and 
dihydrotestosterone (DHT) (Yepuru et al., 2013). 
Higher expression of AKR1C3 enhances survival of 
prostate cancer cells and formation of endothelial 
cell tubes, and is positively correlated with a higher 
Gleason score (Dozmorov et al., 2010). However, 
there were lower expressions of AKR1C3 in AA 
prostate cancers than in CA prostate cancers, 

which suggests a contradictory function of AKR1C3 
in racial disparities between AA and CA men.  
CYP3A5, which is involved in hydroxylation of 
testosterone and dehydroepiandrosterone 
(Zeigler-Johnson et al., 2013), enhances growth of 
prostate cancer cells through facilitating the 
nuclear translocation of AR (Mitra and Goodman, 
2015). The higher expression CYP3A5 in AA men 
may be associated with higher AR levels and a 
higher risk of prostate cancer (Singh et al., 2017). 
As shown here, there were higher expression levels 



 
 
 
 
 

 
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of CYP3A5 in AA prostate cancers compared with 
CA prostate cancers, supporting the previous 
observation and hypothesis.  
In the gonads and adrenals, CYP17A1 is involved in 
various pathways of androgen biosynthesis 
(Bremmer et al., 2014). Although greater 
expression of CYP17A1 appears to correlate with 
higher stages and shorter relapse-free times in 
prostate cancer (Bremmer et al., 2014; Gomez et 
al., 2015; Salvi et al., 2016), expression of the 
CYP17A1 gene was lower in primary prostate 
cancers than in normal prostate tissue and was 
lower in AA prostate cancers than in CA prostate 
cancers. Although, for AA men, a dysfunction of 
CYP17A1 may affect the susceptibility to prostate 
cancer, the present data do not support the 
concept that CYP17A1 is a regulator for racial 
disparities between AA men and CA men. 
HSD3B2 is involved in catalyzing androstendione 
and DHT metabolites (Simard et al., 1996). Higher 
expression of HSD3B2 accelerates the degradation 
of DHT metabolites and leads to lower DHT levels 
(Simard et al., 1996). However, the relationship 
between high DHT levels and prostate cancer risk 
is controversial. For CA men and AA men, there 
are no significant differences in DHT levels in sera 
and tissues (Singh et al., 2017). The present data 
also showed higher expression of HSD3B2 in AA 
prostate cancers compared with CA prostate 
cancers, results that are inconsistent with racial 
disparities between AA and CA men. 
SRD5A2 is responsible for the conversion of 
testosterone into DHT (Fang et al., 2017). Genetic 
analyses suggest that there are SRD5A2 TA repeat 
alleles in AA men at high risk for prostate cancer 
but not in CA men (Singh et al., 2017), indicating 
that genetic variants of SRD5A2 may be associated 
with racial disparities. Variants of the enzyme may 
enhance the activity and result in higher levels of 
DHT, leading to cancer progression. However, 
higher expression of SRD5A2 appears to be 
inconsistent with higher levels of DHT (Singh et al., 
2017). The present data showed that expression of 
SRD5A2 was lower in AA prostate cancers 

compared with those of CAs, which does not 
support a role of SRD5A2 in the racial disparities 
between AA men and CA men. 
In the androgen biosynthesis pathway, UGT2B15 is 
a regulator for androstenedione glucuronidate 
(Gauthier-Landry et al., 2015). High 
androstenedione levels may require more 
glucuronosyltransferases encoded by UGT2B15 
(Singh et al., 2017). Of note, there are higher 
androstenedione levels in normal prostate tissues 
and greater expression of UGT2B15 in AA prostate 
cancers than in those of CAs (Singh et al., 2017). As 
shown here, there was higher expression of 
UGT2B15 in AA prostate cancers compared with 
CA prostate cancers, supporting a function of 
UGT2B15 in racial disparities of prostate cancers.  
Since prostate cancer is a pathophysiologic 
disease involving a variety of genetic factors 
(Chang et al., 2014; Cooper and Page, 2014), the 
change of a single gene may be insufficient to 
produce racial disparities. Further, the functions of 
genes in racial disparities in prostate cancer are 
associated with mRNA and protein expression. 
Moreover, the AA cohort of prostate cancers in 
this TCGA database includes only six cases, which 
limits the statistical power to detect significant 
differences in our analysis. Therefore, a larger 
sample cohort is needed to establish the 
relationship between the genes and racial 
disparities in prostate cancer. 
In summary, in the United States, the incidences of 
prostate cancer are different for CA and AA men. 
Genes, such as CYP3A5 and UGT2B15, which are 
involved in androgen metabolism, appear to be 
associated with racial disparities between AA and 
CA prostate cancers. Due to a limitation of sample 
size, however, the results need to be validated in 
further studies. 

Acknowledgements 
We thank Dr. Donald L. Hill for editorial assistance 
in preparing this manuscript. This work was 
supported by the National Institutes of 
Health/National Cancer Institute (CA179282 and 



 
 
 
 
 

 
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CA118948) and the Department of Defense 
(PC130594 and PC140308). 
 
Conflict of interest statement 
The author has declared that no competing or 
conflict of interests exist. The funders had no 
role in study design, writing of the manuscript 
and decision to publish.    
 
Authors’ contributions 
WL performed the analyses. RL and LW wrote the 
manuscript. 

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