29 96
established
risk
factors
associated with
PCa
are
age,
race,
and
family history,
although
large
geographic
variations
in
PCa
risk
suggest
that
lifestyle
and
environmental
factors
may
also
contribute
to
its
etiology
[3] .It
has
been
hypothesized
that
the
increased
prevalence
of metabolic
syndrome
resulting
from
lifestyle changes associated with a
Western
lifestyle
(including
physical
inactivity
and
higher
intakes
of
refined
carbohydrates
and
excess
calories) may
explain,
in
part,
the
fact
that
once
Asians migrate
to
the
United
States,
their
risk
of
PCa
approaches
that
of
white
Americans within
one
or
two
generations
[4–6].
There
is
little
evidence
for
any
association
between
alcohol
and
prostate
cancer
[7].
Paradoxically,
several
studies
have
reported
an
inverse
association
between
diabetes mellitus
and
prostate
cancer
risk
[8,9].
Cigarette
use
is
the
leading
cause
of
death
from
cancer,
but
the
relationship
between
smoking
and
PCa
remains
controversial;
some
studies
indicate no association, where-
as
others
suggest
an
elevated
risk
among
smokers
[10] .A
recent
meta-analysis
found
a
modest
but
statistically
significant
association
between
cigarette
smoking
and
PCa
death;
a
dose-response
relationship
was
also
found.
Conversely,
the
association
between
cigarette
smoking
and PCa
incidence was mixed
[11]. Smoking may also have a
significant effect on treatment outcome of cancers
for which
smoking
is not
related
[12]. As such,
there has been growing
interest
in
the
field as
to whether patients with a history of
smoking
present with worse
disease,
have worse
response
to
treatment,
or have
other
confounding
factors
that
could
explain
inferior
outcomes
[12] .The
possibility
of
modifying
environmental
factors,
including smoking, have been proposed as a new
frontier
in
the
prevention
and
management
of
several
cancers
including
PCa
[13] .In
this
review we
evaluate
contempo-
rary
evidence
regarding
smoking
as
a
causative
factor
in
PCa
development
and
as
a
significant
variable
in
disease
outcome. We
also
discuss
the
potential
clinical
implica-
tions
of
this
evidence
and
suggest
directions
for
future
research.
2.
Evidence
acquisition
A
search
of
the National Center
for Biotechnology
Informa-
tion
PubMed
database
for
relevant
articles
published
between
2004
and
September
2014
was
performed
by
combining
the
following
PICO
(patient
population,
inter-
vention,
comparison,
outcome)
terms:
male,
smoking,
pros-
tate,
prostate
cancer,
prevention,
diagnosis,
treatment
,
and
prognosis.
Only
articles
published
in
the
English
language
were selected. In addition, sources in the reference sections of
the
identified
publications
were
also
added
to
the
list.
Evidence was not
limited
to human data; data
from
animal
studieswere also
included
in the review. Each article title and
abstract
was
reviewed
for
relevance
and
appropriateness
with
regard
to
the
relationship
between
cigarette
smoking
and
PCa.
Preferred
Reporting
Items
for
Systematic
Reviews
and
Meta-Analysis
guidelines
were
followed
to
ensure
transparent and complete reporting of this systematic review
( Fig. 1). Details of
the
selected
references are
summarized
in
Tables 1 and 2.
3.
Evidence
synthesis
3.1.
The
burden
of
smoking
behavior
Native
Americans
were
using
tobacco
products
in
the
Americas
prior
to
the
arrival
of
Columbus,
but widespread
use of
tobacco
in cigarettes
is more
recent, occurring
largely
during
the
20th
century
[47].
Concern
among members
of
the
scientific
community
that
cigarette
smoking
caused
disease
grew with
the
publication
of
retrospective
epide-
miologic
studies
of
lung
cancer
in
the
late
1940s
and
early
1950s.
Currently,
tobacco
smoking
is
considered
a major
public
health
concern
because
it
is
responsible
for
high
levels
of
mortality
and
morbidity
worldwide.
Smoking
causes
increased
risk
of
mortality
from
lung
cancer
and
aerodigestive,
bladder,
and
several
other
cancers;
it
is
also
associated with
an
increased
risk of
cardiovascular disease,
stroke,
chronic
respiratory
disease,
and
a
number
of
other
medical
conditions
[48].
In
the
developed world,
smoking
was
reported
to
be
the
risk
factor
with
the
largest
attributable mortality
and
attributable
disability-adjusted
life years
(DAYLS) by
the World Health Organization: 12.2%
of all DALYS were attributed
to
smoking. Most of
the deaths
attributable
to
smoking may
be
grouped
into
three
broad
categories: cancers, cardiovascular diseases, and respiratory
diseases. Data
from
Canada
showed
that
cancer
accounted
for
46.8%
of
smoking-attributable
death,
cardiovascular
disease
accounted
for
27.6%,
and
respiratory
diseases
accounted
for
22.3%
[48].
Notwithstanding
the
related
morbidity
and
mortality
and all of
the prevention campaigns and
smoking-cessation
counseling
programs
conducted
in
the
last
50
yr,
the
number
of
daily
smokers
and
total
cigarettes
consumed
each
year worldwide
is
increasing.
There
is
a
continuous
increase
in
the
number
of men
and
women
who
smoke
daily,
increasing
form 721 million
(95%
confidence
interval
[CI],
700
million–742
million)
in
1980
to
967
million
(95%
CI,
944
million–989
million;
p
= 0.001)
in
2012.
Between
1980
and
2012,
the
number
of
cigarettes
smoked
worldwide
increased
from
4.96
trillion
(95%
CI,
4.78
trillion–5.16
trillion)
to
6.25
trillion
(95%
CI,
6.07
trillion–6.44
trillion;
p
= 0.001).
Estimated
prevalence
of
daily
smoking
also
varies
according
to
different
geographic
area,
from
>
50%
in Western
Europe
and
Asia
(Russia,
Armenia,
Indonesia)
to
27.5–34.7%
in
Central
Europe
(France,
Spain, Germany); 16.5–19.7%
in
the United
States, Canada,
and Brazil;
and
<
10%
in
sub-Saharan Africa
(Niger, Nigeria, Ghana,
Sudan)
[49].
Possible
differences
in
smoking
behavior
should
be
considered when
comparing
PCa
data
from
different
geographic
areas.
3.2.
Association
between
smoking
and
prostate
cancer
3.2.1.
Potential
biological mechanisms
Some
studies
have
shown
possible mechanistic
pathways
linking
smoking and PCa development and progression, but
E U R O P E A N
U R O L O G Y
F O C U S
1
( 2 0 1 5
)
2 8 – 3 8
29