Prostate(Cancer(

in(Black(Men(
Arnelle Downing1
Date Submitted: 10/26/17
ENGw3307
Project 1 First Draft
AMA Citation Style
Word Count: 2503

Abstract(

Introduction(

A look into the literature of the past few decades shows distinctive health disparities between
African American men and their White counterparts. Consistently, black men have ranked the lowest of
all groups in the US in regard to health3. Overarching evidence has concluded that Black men are
disproportionately more likely to die from undiagnosed or poorly managed chronic conditions than
white men; this is particularly true for prostate cancer.

Prostate cancer is the 2nd most common cancer among men. In the United states, it is the 3rd
most fatal cancer among men in the United States7. 1 in 7 men will be diagnosed with prostate cancer
during his lifetime and approximately 1 in 39 men will die of it7. However, of this portion, black men
have a higher representation.
In regard to prostate cancer, Black men have the highest incidence and mortality rate of all groups of
men2. In comparison to white men, black men have an incidence that is approximately 60% higher and a
mortality rate that is 2 to 3 times higher6, 72%9. Over the years, studies have been conducted to
determine the underlying cause(s) of these disparities. Common factors that have been explored include
genetic, environmental, and socioeconomic, difference in attitude towards healthcare, access to
healthcare2, lower income, education, lack of health insurance, and co-morbidities9. While some of these
studies only examined correlations factor by factor, some did investigate the effects of intersectionalities
on incidence and morbidity rates. A study conducted by Taksler et al. found that approximately 76% of
the mortality gap is due to higher incidence of prostate disease in African American men; 45% from
local/regional prostate cancer, 26% from metastatic prostate cancer, and 5% from unstaged tumors. The
remaining 24% of the mortality gap is due to higher mortality conditional on diagnosis9.
This review provides insight into the mechanisms in which factors, varying from biological to
cultural, contribute to the incidence and morbidity rate disparities between black and white men.

Factors(
!
Biological(

Men of African ancestry have difference in pathological features than white men11. Based on similar
incidence and mortality rates men of African descent across the world, it is clear than genetics plays a
major role.

Genotype and Androgen expression

The progression of prostate cancer in black men is significantly higher than that of white men.
An autopsy study of 1,056 men reported that black men had increased volume of cancerous tissue.
Consequently, prostate cancer escalates to achieve distant metastasis at a proportion of 4:1 for black men
in comparison to white men6. But why is this? In recent studies, the Androgen receptor (AR) pathway
has been found to play a critical role in prostate cancer health disparities. This pathway is present in the
development, function and homeostasis of the prostate4. Polymorphisms in genes associated with this
pathway are found in black men in higher quantities than in white men.

Multiple risk alleles stemming from race/ethnic related single nucleotide polymorphisms (SNPs)
are associated with prostate cancer. CYP3A4 is a protein involved in the transformation of testosterone
to metabolites. Inhibition of this process ultimately increases androgen receptor stimulation (Influence of
androgen receptor expression on prostate cancer will be further discussed in the next section).
Inhibition can be caused by germline genetic variations on chromosome 7; these allelic variants are
CYP3A4*1B and CYP3A4-V. The allele frequency of these variants varies between white and black
men, with 8% of white men and 83% of black men having 1 or more copies6.

Black men with prostate cancer have a higher prevalence of a thymine and adenine (TA) repeat
sequence as well as A49T allelic variants of the SRD5A2 gene. These polymorphisms encode for a type

2
II 5-alpha-reductase that has higher conversion activity12. 5-alpha reductase activity converts
testosterone to dihydrotestosterone (DHT), meaning more activity corresponds with increased levels of
DHT. DHT has a higher binding affinity to androgen receptors than testosterone, and therefore activates
more target genes at lower concentrations than testosterone4.

Other Pathways
There are additional cancer-associated pathways such as Wnt/beta-catenin, PI3K/AKT, VEGF
and IGF-1 signaling pathways that are statistically overrepresented with differentially expressed genes in
black men compared to white men. PI3K/AKT and AR pathways help maintain prostate cancer
proliferation in low-androgen environments. Wnt/beta-catnin is an oncoprotein and transcriptional
coactivator of androgen receptors and has been implicated in advanced and metastatic prostate cancer.
IGF-1 is a growth factor signaling pathway that can also stimulating androgen recptor activation. The
stimulation increased receptor occupancy at target genes and upregulates AR-target gene expression in
prostate cancer cells of black men12. Androgen receptor expression is 81% higher in black males than
white males. Metastasis promoting genes are more highly expressed in the tumors of black males6.

Age
Black patients were younger than white patients9 to die from advanced or metastatic prostate cancer.
Incidence for blacks older than 68 was significantly above than for white men.
(
Environmental
Diet
Levels of cholesterol can be associated with prostate cancer incidence because cholesterol is the
precursor of androgens, acts as a cell proliferation mediator and through inflammatory processes. This
steroidal lipid is synthesized in the liver and prostate. As one gets older, cholesterol synthesis in the
prostate is boosted, resulting in increased accumulation in the prostate11.
Factors contributing to elevated cholesterol levels include diet, obesity and hyper tension. Black
men have higher fat content diet, higher body mass index and higher rates of hypertension. Mechanisms
associated with these comorbidities are release of inflammatory cytokines and reactive oxides that result
in oxidative stress, DNA damage and cell proliferation. They also upregulate androgen receptor protein
expression6.

Socioeconomic(
Income
Income showed negative correlation to incidence of metastasis for black men. Black men
representing the poorest income quartile had a 24-40% higher metastatic incidence rate than those in
wealthier quartiles. More specifically, black men living in areas where the median income is less than
$25,000 had higher metastatic incidence that those in the second-poorest quartile by 38% for whites and
27% for blacks9.

Healthcare(
Access to PSA Testing
The Prostate Specific Antigen (PSA) Test is a blood test primarily used to screen for prostate
cancer. This test was approved in 1986 to monitor progression of cancer in already diagnosed patients.

3
In 1994, the test was further approved to be used in concurrence with a digital rectal exam to test
undiagnosed men. The test detects for levels of PSA levels in the blood. High levels of PSA detected in
the blood can indicate prostate cancer as well as other conditions such as presence of malignant tumors,
or enlarged or inflamed prostate8. This lack of specificity has led to many conflicting opinions
concerning PSA testing.
Only about 25% of men who undergo prostate biopsies after PSA testing actually have prostate
cancer8. Therefore, risk of false-positives, false-negatives, and overtreatment are associated with PSA
testing9. However, there is undeniable evidence that use of PSA testing has contributed to the lesser
proportion of men presenting with advanced prostate cancer. Specifically, regular testing is associated
with lower incidence of metastatic prostate cancer and higher incidence of local/regional disease across
the board9. A study conducted by Taksler et. al showed that occasional screening (1 test in 3 years)
instead of annual testing lowered metastatic incidence substantially for black men9.
Interestingly, there is evidence that contradicts the preceding statement; evidence that suggests
that between white and black men, black men disproportionately present more advanced disease
symptoms9. This alone contributes to their higher mortality rate. However, there is some congruence
here in respect to treatment disparities.

Treatment

Treatment differences contribute significantly to survival disparities. Black men are less likely to
be treated for prostate cancer than white men6. For localized cancer, Black men are less likely to receive
definitive treatment than white men5. This may be considered a lack of attention to personal health, but
this perception needs to be revamped.

Lack of pursuance of a treatment plan has more recently been associated with in fear of
diagnosis, distrust of the physicians6, and overall adherence to traditional gender norms of masculinity3
by black men. Data provided by Taskler et. Al show significant differences between masculine
conventions is at the top of this list because across ethnicities, men are 24% less likely than women to
have had a doctors appointment in the last year3. Out of that 24%, black men across income quartiles
are 50% less likely to have seen a physician within the past year. The reasoning behind these statistics
are purely speculative with little empirical evidence to back them up. These reasonings include that 1)
more black men are incarcerated and once out of jail have a hard time finding jobs that will provide
them with healthcare benefits, such as insurance 2) low income men try to be more masculine and
therefore dont want to compromise their manhood 3) conception the health care providers want to take
advantage of them3.

Conclusion(
The complexity of the ways in which biological, environmental, socioeconomic, cultural, and behavioral
forces needs to be further explored by researchers. It is clear that for black men, there is no lone factor as
the cause of increased incidence and mortality rates in regard to prostate cancer. That is due to lack of

4
understanding of the basis of the black mans health profile. With the help of this literature review,
which includes a compilation of articles ranging from 2000 to the present, strides can be made to lessen
the gap and save the lives of black men with prostate cancer. Scientists and health care providers need to
establish a way to infiltrate communities of lower income and socioeconomic status, gain the trust of
those residents, educate and inform them on preventative behaviors, persuade them to get tested starting
at a younger age, and offer them a variety of treatment options. Obviously, this cannot happen overnight.

Acknowledgements(
This article was inspired by my grandfather who just one year ago passed away from metastatic prostate
cancer. Prior to doing this research, I had never learned much about his condition. However, I very
vividly recall the trials and tribulations he endured for almost two years of chemotherapy, radiation, and
prescription drugs. In the end, he decided he no longer wanted to fight his battle, and passed away
before I got to say goodbye. It is clear to me now that there were ways in which this could have been
avoided. Therefore, I dedicate this to black men of all ages. Please stay informed.

5
 Annotated Bibliography

1.! Chu K, Tarone R, Freeman H. Trends in Prostate Cancer Mortality among Black Men and White
Men in the Unites States. Cancer. 2003;97(6):1507-1516. Found via Web of Science search. A
study that investigates race , age, and frequency of PSA testing as possible variants of the
declining prostate mortality rates in the US.
2.! Freedland S, Sutter M, Naitoh J, Dorey F, Csathy G, Aronson W. Clinical Characteristics in
Black and White Men With Prostate Cancer in an Equal Access Medical Center. Urology.
2000;55:387-390. Found via Web of Science search. An older review article that provides intel
of incidence and mortality rates of men with equal access to healthcare.
3.! Gilbert K, Ray R, Siddiqi A, Shetty S, Baker E, Elder K, Griffith D. Visible and Invisible Trends
in Black Men s Health: Pitfalls and Promises for Addressing Racial, Ethnic, and Gender
inequities in Health. Annual Review of Public Health. 2016; 37:295-311. Found via Web of
Science search. A review that delves into that leading causes of death and health disparities for
black men. Examines influences of history, income, masculinity, and institutionalized racism.
4.! Lonergan P, Tindall D. Androgen receptor signaling in prostate cancer development and
progression. Journal of Carcinogenesis. 2011;10:20. doi:10.4103/1477-3163.83937. Found via
PubMed search. A review of the physiology of androgen receptor structure and signaling and its
correspondence with prostate cancer progression.
5.! Mahal B, Chem Y, Muralidhar V, Mahal A, Choueiri T, Hoffman K, Hu J, Sweeney C, Yu J,
Feng F, Kim S, Beard C, Martin N, Trinh Q, Nguyen P. Racial disparities in prostate cancer
outcome among prostate-specific antigen screening eligible population in the United States.
Annals of Oncology. 2017;28:1098-1104. Doi:10.1093/annonc/mdx041. Found via Web of
Science search. This study examines racial disparities in prostate cancer in PSA-screening
eligible populations. Suggests that early diagnosis of prostate cancer in black men will reduce the
mortality rate.
6.! Powell I, Bock C, Ruterbusch Julia, Sakr W. Evidence Supports a Faster Growth rate and/or
Earlier Transformation to Clinically Significant Prostate Cancer in Black Than in White
American Men, and Influences Racial Progression and Mortality Disparity. Urology.
2010;183:1792-1797. Found via Web of Science search. A study that examines biological and
pathological difference between black men and white men to determine cause of disparity. Found
that prostate cancer grows more rapidly in black men due to difference in gene and protein
expression.
7.! Prostate Cancer. Cancer.org. https://www.cancer.org/cancer/prostate-cancer/about.html.
Accessed October 26, 2017. Found via Google search. A comprehensive overview of prostate
cancer, its causes, risks, detection, diagnosis, staging, treatments ad after treatment plans.
8.! Prostate-Specific Antigen (PSA) Test. Cancer.gov. https://www.cancer.gov/types/prostate/psa-
fact-sheet. Accessed October 25, 2017. Found via Google Search. A comprehensive overview of
the PSA test and the pros and cons of its usage since receiving approval by the FDA.
9.! Taksler G, Keating N, Cutler D. Explaining Racial Difference in Prostate Cancer Mortality.
Cancer. 2012:4280-4289. Doi:10.1002/cncr.27379. Found via Web of Science search. This study
explores previously suggested risk factors of prostate cancer in black men to determine
correlation. Found that more frequent PSA testing and more aggressive treatment of prostate
cancer in black men should reduce the mortality gap.

6
 10.!Tsodikov A, Gulati R, Carvalho T, Heijnsdijk E, Hunter-Merrill R, Mariotto A, Koninh H,
Etzioni. Is Prostate Cancer Different in Black Men? Answers From 3 Natural History Models.
Cancer. 2017:2312-2319. Doi:10.1002/cncr.30687. Found via Web of Science search. This study
investigated he higher incidence of prostate cancer in black men utilizing the 3 natural history
models. Found that black men have higher incidence of preclinical disease and higher risk of
metastatic progression.
11.!Tulloch-Reid M, McFarlane-Anderson N, Bennett F, Aiken W, Jackson M. Effects of
cholesterol, C-reactive protein, and interleukin-6 on prostate cancer risk in a population of
African ancestry. Cancer Causes & Control. 2017. Doi:10.1007/s10552-017-0945-4. Found via
Web of Science search. This study explores the effects of cholesterol level sin Caribbean men.
Conclusions stated that heightened cholesterol levels were associated with low-grade prostate
cancer.
12.!Wang B, Yang Q, Ceniccola K, Bianco F, Andrawis R, Jarrett T, Frazier H, Patierno S, Lee N.
Androgen Receptor-Target Genes in African American Prostate Cancer Disparities. Prostate
Cancer. 2013;2013. Found via Web of Science search. A study that details the mechanisms by
which AR signaling and AR expression is are induced and amplified.
13.!Whitney C, Howard L, Amling C, Aronson W, Cooperberg M, Kane C, Terris M, Freedland S.
Race Does Not Predict the Development of Metastases in Men with Nonmetastatic Castration-
Resistant Prostate Cancer. Cancer. 2016:3848-3855. Doi: 10.1002/cncr.30221. Found via Web
of Science search. This study addresses the impact of race on evolution of metastasis in men who
had castration-resistant prostate cancer.