Download Prostate cancer in the African-Caribbean community

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Prostate cancer in the
African-Caribbean community
NIYUKTA THAKARE AND FRANK CHINEGWUNDOH
African-Caribbean men
have the highest risk of
prostate cancer, which is
the second most common
male cancer worldwide. The
authors present an overview
of the epidemiology, genetic
factors and disparities in
management of prostate
cancer in the AfricanCaribbean community.
Australia/New Zealand
Northern America
Western Europe
Northern Europe
Polynesia
Caribbean
More developed regions
Southern Africa
South America
Micronesia
Southern Europe
Central and Eastern Europe
World
Central America
Western Asia
Middle Africa
Western Africa
Eastern Africa
Melanesia
Less developed regions
South-Eastern Asia
Northern Africa
Eastern Asia
South-Central Asia
Incidence (per 100 000)
Mortality (per 100 000)
0
20
40
60
80
100
120
Figure 1. Age-standardised prostate cancer incidence and mortality rates worldwide3
I
Niyukta Thakare, MB BS, MRCS, Research
Registrar in Urology, Barts Health NHS
Trust, London; Frank Chinegwundoh
MBE, MB BS, MS, MML, FRCS(Urol), FEBU,
Consultant Urological Surgeon, Barts
Health NHS Trust; Honorary Visiting
Professor, City University London
www.trendsinmenshealth.com
n the UK, prostate cancer is the most
common male cancer and the second
most common cause of cancer death in
men after lung cancer. In their current
strategy, the UK Department of Health
has addressed the impact of inequalities
on cancer outcomes.1 African-Caribbean
ethnicity is a known risk factor for
prostate cancer. Ethnic disparity in
prostate cancer has become an important
issue worldwide because of the higher
incidence and mortality in the AfricanCaribbean population.
The National Cancer Institute defines ‘cancer
health disparities’ as ‘adverse differences
in cancer incidence (new cases), cancer
prevalence (all existing cases), cancer death
(mortality), cancer survivorship, and burden
of cancer or related health conditions that
exist among specific population groups in
the United States’.2 The focus on identifying
areas of research in ethnic disparity in
prostate cancer is increasing.
We have examined the current knowledge of
epidemiological features and genetic and
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molecular characteristics of prostate cancer in
African-Caribbean men. We also aim to provide
an insight into the existing evidence for
differences in prostate cancer diagnosis and
management between ethnic groups of men.
EPIDEMIOLOGY
The International Agency for Research on
Cancer has assimilated incidence and
mortality data for cancer throughout the
world as part of the GLOBOCAN project.3
In 2012, an estimated 1.1 million men were
diagnosed with prostate cancer worldwide.
A 25-fold variation in incidence rates
is seen globally, with the rates being
higher in the developed world (Figure 1).
Australia/New Zealand has the highest
age-standardised rate of 111.6 per 100 000,
followed by North America and western
Europe. The lowest rates are seen in Asian
countries. The higher incidence rate in
developed countries is mainly attributed
to widespread PSA testing and readily
available diagnostic modalities. In the
Caribbean and South Africa, a relatively
high incidence rate of 79.8 and 61.8 per
100 000 respectively is observed. This is in
spite of the fact that PSA testing is not
very prevalent in these regions.
In contrast, there is only a 10-fold
global variation in mortality rates,
which are predominantly high in less
developed regions. The Caribbean has
the highest age-standardised mortality
of 29 per 100 000, followed by subSaharan Africa (19–24 per 100 000).
Moreover, these are the only countries
where prostate cancer is the leading
cause of death.4 These disproportionate
geographical trends suggest that
ethnicity plays a vital role as a risk factor
in prostate cancer.
According to the US Surveillance,
Epidemiology, and End Results (SEER)
program, the 2000–11 age-standardised
incidence rates for African-American men
are 202.5 per 100 000, the highest in
the world.5 A reduction in incidence
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has been seen after the end of an
‘enthusiastic PSA testing’ era in white as
well as African-American men. Mortality
rates are invariably higher at 44.0 per
100 000 among African-American men in
comparison to 19.2 per 100 000 among
white-American men.
In the UK in 2008–10, the National Cancer
Intelligence Network (NCIN) reported that
incidence and mortality rates for prostate
cancer were 89.0–116.0 and 22.7–23.9 per
100 000, respectively.6 Within the UK,
ethnicity-related epidemiological data are
currently available only for England. The
NCIN has published incidence rates for
ethnic groups of men diagnosed with
prostate cancer in England (2000–06).
Age-standardised incidence rates were
significantly higher in the ‘black’ ethnic
group (120.8–247.9 per 100 000) compared
to the ‘white’ ethnic group (96.0–99.9 per
100 000).7 Mortality statistics related to
ethnicity for 2007–09 show that, in
England, African-Caribbean men have a
30% higher mortality rate compared to
white men.8
In terms of prostate cancer survival, the
global CONCORD study showed a wide
variation in rates from 40% to 95%
throughout the world.9 SEER data
(1998–2010) show that African-American
men have lower 5-year relative survival
rates than their white counterparts
(95.7% versus 99%).10 However, in the UK,
no significant differences in survival have
been seen.7 The reported relative survival
rates in England are in fact higher for men
of ‘black’ ethnicity (Table 1).
should be considered before drawing
inferences regarding ethnic disparities in
epidemiological research.
BIOLOGICAL FACTORS
The presumed factors contributing to
ethnicity-related differences are socioeconomic status, cultural beliefs and
genomic differences. Ongoing research
in the field of genetic and molecular
basis for prostate cancer disparity in
African-American men has identified the
following areas:11,12
• inherited risk alleles
• tumour genes
• androgen receptors
• epigenetics.
Genome-wide association studies have
identified single nucleotide polymorphisms
(SNPs) on several gene loci and
chromosomes in prostate cancer. This
genetic inheritance has been studied
to explain the differences in tumour
biology in African-American and white
men. Multiple SNPs within the 8q24
region are known to confer increased risk
Age (years)
AfricanCaribbean
White
1-Year relative survival (%)
15–64
98.3
96.5
65–99
94.0
89.7
15–99
95.6
91.7
Agestandardised
93.6
92.0
3-Year relative survival (%)
It is challenging to interpret and compare
data from various sources, mainly
because of variations and limitations
in methodology of epidemiological
studies. Cancer cases are also likely to
be under-reported in the less developed
countries. Moreover, ethnicity recording
itself is not robust or accurate and
under-representation of African-Caribbean
groups is common. These shortcomings
15–64
91.7
88.4
65–99
84.8
77.7
15–99
87.5
81.0
Agestandardised
83.7
80.7
Table 1. Relative survival of African-Caribbean and
white men in the UK7
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of prostate cancer in African-American
men.13 SNPs within the CYP3A4 gene cause
a genetic variant CYP3A4*1B, which is
associated with aggressive characteristics
in African-American men diagnosed with
prostate cancer.14
TMPRSS2 is an androgen-responsive
protease specific to prostate cells and
ERG is an ETS (E-twenty six) related gene.
TMPRSS2-ERG fusions have also been
studied to explain the differences in
prostate cancer in African-American and
white men.15 EphB2 tyrosine kinase, a
prostate cancer tumour-suppressor gene,
is thought to be associated with increased
risk of prostate cancer in African-American
men.16 Genomic gains and losses relevant
to oncogene function have been studied by
detection of copy number variations and
show higher amplification in prostate
tumours of African-American men.17
The role of androgen receptor (AR)
gene structure and function has been
investigated in several studies. It has
been reported that fewer CAG repeats
in the AR gene contribute to higher
AR activity in African-American men,18
although evidence to the contrary also
exists.19 Higher genomic AR function
leading to higher levels of AR proteins in
African-American men is also reported.20
Epigenetic changes, including glutathione
S-transferase-pi gene (GSTP1)
hypermethylation, are observed in prostate
cancer tissue, although similar levels have
been observed between African-American
and white men.21 On the other hand,
regulatory genes including TIMP3 and
NKX2–5 are more likely to be methylated
in African-American men.22 Reduced
signalling of vitamin D pathway-related
genes including vitamin D receptors is
considered to be associated with higher
risk in African-American men.23
Unfortunately, the exact role of these
molecular factors is not yet established
and the majority of these studies include
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African-American men. However, these
early attempts have provided a direction
for future research and advances.
MANAGEMENT AND OUTCOMES
The management pathway of prostate
cancer starts at the detection stage.
Screening is a controversial issue and,
although selective screening of high-risk
groups seems reasonable, screening studies
focused on ethnic minorities are lacking.
In the large screening trials, including the
Prostate, Lung, Colorectal and Ovarian
(PLCO) Cancer Screening Trial, which
constitute the existing evidence, ethnic
groups including African-Caribbean men
were under-represented.24 There is an
ongoing argument for selective screening
of African-Caribbean groups25 and it
remains to be seen whether it will become
common practice.
In the UK, the Prostate Cancer in Ethnic
Subgroups (PROCESS) study investigated
differences in prostate cancer between
African-Caribbean and white men.26 The
study comprised a retrospective cohort of
men diagnosed with prostate cancer in the
London and Bristol areas over a 5-year
period. It concluded that African-Caribbean
men were at a substantially higher risk of
developing prostate cancer compared to
white men, especially in the younger age
group. Several studies, particularly in the
US, have queried the differences in disease
presentation, tumour stage and tumour
burden among ethnic groups. A systematic
review of these disparities revealed that
African-American men present at a
younger age and also have higher-risk
disease and higher tumour volumes.27
cancer in these men.28 However, the
quality of evidence contributing to this is
far from adequate. It is also somewhat
contradictory given the higher rates of
pathological upgrading after radical
prostatectomy in African-American
men with low-risk disease.29 Moreover,
adverse oncologic outcomes and lower
biochemical recurrence-free survival are
also reported after radical prostatectomy
in African-American men.30
Despite persistent efforts to tackle these
issues, there are still significant mortality
differences in prostate cancer among
ethnic groups. In fact a recent study
comprising the SEER data in the US
showed that there has been no reduction
in disparity in prostate cancer mortality
in African-American men over the past
20 years.31 This means that more needs to
be done to identify and narrow the gap in
current management of prostate cancer in
African-Caribbean men in order to achieve
discernible results.
SUMMARY
There is undoubtedly a disparate burden of
prostate cancer in the African-Caribbean
community. Mounting evidence indicates
that prostate cancer in African-Caribbean
men is a biologically distinct entity. Further
research into biological determinants is
required to determine the exact cause of
these disparities. There is a crucial need to
conduct larger outcome-related studies and
establish new pathways to improve prostate
cancer care in African-Caribbean men.
Declaration of interests: none declared.
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