An Update on Occupation and Prostate Cancer REVIEW An Update on Occupation and Prostate Cancer
16
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014 501 DOI:http://dx.doi.org/10.7314/APJCP.2014.15.2.501 An Update on Occupation and Prostate Cancer Asian Pac J Cancer Prev, 15 (2), 501-516 Introduction Epidemiological research on prostate cancer is difficult because of the large proportion of men who, with increasing age, will develop prostatic tumours of low malignant potential that will have no discernible effect on a man’s health or longevity. This presents a problem because many ageing men will develop lower urinary tract symptoms (LUTS) related to benign prostatic hypertrophy (BPH) which when investigated and treated by trans- urethral resection of the prostate (TURP) foci of prostatic adenocarcenoma will be identified in the tissue removed by this procedure. Thus, increased medical surveillance, common for many occupational cohorts, is likely to result in increased prostate cancer diagnosis compared with the general male population. This problem has been exacerbated since the advent of prostate specific antigen (PSA) testing two decades ago which has led to gross over diagnosis of tumours that otherwise would have remained undetected. It follows that epidemiological studies of prostate cancer must take into account, where possible, some index of tumour aggressiveness and potential to progress to invasive disease. For an overview of references on the background to Prostate Cancer and occupational exposure, see Tables 1 for reviews and for research studies. The topic of principal interest to public health practitioners is the question of the causes of clinically significant prostate cancer and the identification of potentially avoidable risk factors that men encounter in their everyday lives. It is necessary to answer the question: 1 Department of Epidemiology and Preventive Medicine, Monash University, The Alfred, 2 Cancer Epidemiology Centre, Cancer Council Victoria, 3 Centre for Genetic Epidemiology, University of Melbourne, Melbourne, Australia *For correspondence: [email protected] Abstract Background: Our aim was to identify gaps and limitations in the current literature and to make recommendations for future research required to address these. Materials and Methods: We reviewed occupational exposures and related factors associated with the risk of prostate cancer between 2000 and 2012. These included chemical, ergonomic, physical or environmental, and psychosocial factors which have been reported by epidemiological studies across a range of industries. Results: The results are inconsistent from study to study and generally this is due to the reliance upon the retrospectivity of case-control studies and prevalence (ecological) studies. Exposure assessment bias is a recurring limitation of many of the studies in this review. Conclusions: We consider there is insufficient evidence to implicate prostate cancer risk for ergonomic, physical, environmental or psychosocial factors, but there is sufficient evidence to implicate toxic metals, polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs). More research is required to identify specific pesticides that may be associated with risk of prostate cancer. Keywords: Occupational exposure - risk - risk factors - maximum allowable concentrations - threshold - prostate cancer REVIEW An Update on Occupation and Prostate Cancer Glenn Doolan 1 *, Geza Benke 1 , Graham Giles 1,2,3 what constitutes harmful exposure to certain substances or experiences in relation to men’s occupations? Greater levels of prevention will then lead to a reduction in the incidence, morbidity and consequent mortality from prostate cancer. The importance of such research can be underscored by the fact that prostate cancer was the 4 th ranking cause of cancer death and the 3 rd highest for cancer incidence for men in Victoria in 2008 (Thursfield et al., 2010). The median age at diagnosis was 67 years (Thursfield et al., 2011b). The incidence rate in 2010 was 115.4 per 100,000 men and the mortality rate was 13.3 per 100,000 men (Thursfield et al., 2011a). Five year survival in Victoria is 91% (Thursfield et al., 2012). In comparison, the median overall survival in Canada for intermittent therapy is 8.8 years and continuous therapy 9.1 years (Crook et al., 2012). It is not known what causes prostate cancer, the only established risk factors being age, race (African and Caribbean) and having a family history of prostate cancer. Over the last two decades, researchers have investigated a range of risk factors (Bostwick et al., 2004) that includes the intensity of exposures to a range of hazardous chemicals (Sharma-Wagner et al., 2000; Achanzar et al., 2001) including genetic factors (Cui, 2001), alcohol consumption (Lumey et al., 1998) (not in the time period but included as a starting point and for completeness), the impact of smoking over time (Giles et al., 2001), sexual activity (Dennis and Dawson, 2002), early growth, body size and body mass index (Giles et al., 2003) , and to radiation (Gershkevitsh et al., 2002) (Table 1). Also,
Transcript of An Update on Occupation and Prostate Cancer REVIEW An Update on Occupation and Prostate Cancer
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014 501
DOI:http://dx.doi.org/10.7314/APJCP.2014.15.2.501An Update on Occupation and Prostate Cancer
Asian Pac J Cancer Prev, 15 (2), 501-516
Introduction
Epidemiological research on prostate cancer is difficult because of the large proportion of men who, with increasing age, will develop prostatic tumours of low malignant potential that will have no discernible effect on a man’s health or longevity. This presents a problem because many ageing men will develop lower urinary tract symptoms (LUTS) related to benign prostatic hypertrophy (BPH) which when investigated and treated by trans-urethral resection of the prostate (TURP) foci of prostatic adenocarcenoma will be identified in the tissue removed by this procedure. Thus, increased medical surveillance, common for many occupational cohorts, is likely to result in increased prostate cancer diagnosis compared with the general male population. This problem has been exacerbated since the advent of prostate specific antigen (PSA) testing two decades ago which has led to gross over diagnosis of tumours that otherwise would have remained undetected. It follows that epidemiological studies of prostate cancer must take into account, where possible, some index of tumour aggressiveness and potential to progress to invasive disease. For an overview of references on the background to Prostate Cancer and occupational exposure, see Tables 1 for reviews and for research studies. The topic of principal interest to public health practitioners is the question of the causes of clinically significant prostate cancer and the identification of potentially avoidable risk factors that men encounter in their everyday lives. It is necessary to answer the question:
1Department of Epidemiology and Preventive Medicine, Monash University, The Alfred, 2Cancer Epidemiology Centre, Cancer Council Victoria, 3Centre for Genetic Epidemiology, University of Melbourne, Melbourne, Australia *For correspondence: [email protected]
Abstract
Background: Our aim was to identify gaps and limitations in the current literature and to make recommendations for future research required to address these. Materials and Methods: We reviewed occupational exposures and related factors associated with the risk of prostate cancer between 2000 and 2012. These included chemical, ergonomic, physical or environmental, and psychosocial factors which have been reported by epidemiological studies across a range of industries. Results: The results are inconsistent from study to study and generally this is due to the reliance upon the retrospectivity of case-control studies and prevalence (ecological) studies. Exposure assessment bias is a recurring limitation of many of the studies in this review. Conclusions: We consider there is insufficient evidence to implicate prostate cancer risk for ergonomic, physical, environmental or psychosocial factors, but there is sufficient evidence to implicate toxic metals, polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs). More research is required to identify specific pesticides that may be associated with risk of prostate cancer. Keywords: Occupational exposure - risk - risk factors - maximum allowable concentrations - threshold - prostate cancer
REVIEW
An Update on Occupation and Prostate CancerGlenn Doolan1*, Geza Benke1, Graham Giles1,2,3
what constitutes harmful exposure to certain substances or experiences in relation to men’s occupations? Greater levels of prevention will then lead to a reduction in the incidence, morbidity and consequent mortality from prostate cancer. The importance of such research can be underscored by the fact that prostate cancer was the 4th ranking cause of cancer death and the 3rd highest for cancer incidence for men in Victoria in 2008 (Thursfield et al., 2010). The median age at diagnosis was 67 years (Thursfield et al., 2011b). The incidence rate in 2010 was 115.4 per 100,000 men and the mortality rate was 13.3 per 100,000 men (Thursfield et al., 2011a). Five year survival in Victoria is 91% (Thursfield et al., 2012). In comparison, the median overall survival in Canada for intermittent therapy is 8.8 years and continuous therapy 9.1 years (Crook et al., 2012). It is not known what causes prostate cancer, the only established risk factors being age, race (African and Caribbean) and having a family history of prostate cancer. Over the last two decades, researchers have investigated a range of risk factors (Bostwick et al., 2004) that includes the intensity of exposures to a range of hazardous chemicals (Sharma-Wagner et al., 2000; Achanzar et al., 2001) including genetic factors (Cui, 2001), alcohol consumption (Lumey et al., 1998) (not in the time period but included as a starting point and for completeness), the impact of smoking over time (Giles et al., 2001), sexual activity (Dennis and Dawson, 2002), early growth, body size and body mass index (Giles et al., 2003) , and to radiation (Gershkevitsh et al., 2002) (Table 1). Also,
Glenn Doolan et al
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014502
0
25.0
50.0
75.0
100.0
New
ly d
iagn
osed
with
out
trea
tmen
t
New
ly d
iagn
osed
with
tre
atm
ent
Pers
iste
nce
or r
ecur
renc
e
Rem
issi
on
Non
e
Chem
othe
rapy
Radi
othe
rapy
Conc
urre
nt c
hem
orad
iatio
n
10.3
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12.8
30.025.0
20.310.16.3
51.7
75.051.1
30.031.354.2
46.856.3
27.625.033.130.031.3
23.738.0
31.3
0
25.0
50.0
75.0
100.0
New
ly d
iagn
osed
with
out
trea
tmen
t
New
ly d
iagn
osed
with
tre
atm
ent
Pers
iste
nce
or r
ecur
renc
e
Rem
issi
on
Non
e
Chem
othe
rapy
Radi
othe
rapy
Conc
urre
nt c
hem
orad
iatio
n
10.3
0
12.8
30.025.0
20.310.16.3
51.7
75.051.1
30.031.354.2
46.856.3
27.625.033.130.031.3
23.738.0
31.3
0
25.0
50.0
75.0
100.0
New
ly d
iagn
osed
with
out
trea
tmen
t
New
ly d
iagn
osed
with
tre
atm
ent
Pers
iste
nce
or r
ecur
renc
e
Rem
issi
on
Non
e
Chem
othe
rapy
Radi
othe
rapy
Conc
urre
nt c
hem
orad
iatio
n
10.3
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12.8
30.025.0
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51.7
75.051.1
30.031.354.2
46.856.3
27.625.033.130.031.3
23.738.0
31.3
Tabl
e 1.
Risk
-fact
or R
evie
ws a
nd R
isk-fa
ctor
Stu
dies
Risk
-fact
or R
evie
ws
Rev
iew
Cou
ntry
M
etho
dFi
ndin
gs/ O
R(9
5%C
I)Su
mm
ary
Den
nis e
t al.,
(200
2)
USA
Met
a Ana
lysi
s36
inde
pend
ent S
tudi
es
Ove
rall
RR
=1.4
; 95%
CI=
1.2-
1.7
Syph
ilis R
R=2
.3; 9
5%C
I=1.
3- 3
.9In
crea
sing
no.
of s
exua
l par
tner
sR
R=1
.2; 9
5%C
I=1.
1-13
7
The
data
sugg
est a
n el
evat
ed re
lativ
e ris
k of
pro
stat
e ca
ncer
am
ong
men
with
a h
isto
ry o
f sex
ually
tran
smitt
ed in
fect
ions
. Th
e ris
k is
als
o as
soci
ated
with
an
incr
easi
ng fr
eque
ncy
of se
xual
act
ivity
, and
an
incr
ease
d nu
mbe
r of s
exua
l par
tner
s. Th
e da
ta d
oes n
ot su
ppor
t ass
ocia
tions
with
mul
tiple
mar
riage
s, ag
e at
firs
t int
erco
urse
, or a
ge a
t firs
t mar
riage
. It i
s sug
gest
ed
that
infe
ctio
ns m
ay re
pres
ent o
ne m
echa
nism
thro
ugh
whi
ch p
rost
ate
canc
er d
evel
ops.
Bos
twic
k et
al.,
(200
4)U
SAIn
dep
th R
evie
w15
46 R
efer
ence
cita
tions
This
revi
ew is
a c
onte
mpo
rary
and
com
preh
ensi
ve, l
itera
ture
-bas
ed a
naly
sis o
f the
put
ativ
e ris
k fa
ctor
s for
hum
an p
rost
ate
canc
er. P
rost
ate
canc
er h
as th
e hi
ghes
t pre
vale
nce
of a
ny n
on-s
kin
canc
er in
the
hum
an b
ody,
with
sim
ilar l
ikel
ihoo
d of
ne
opla
stic
foci
foun
d w
ithin
the
pros
tate
s of m
en a
roun
d th
e w
orld
rega
rdle
ss o
f die
t, oc
cupa
tion,
life
styl
e, o
r oth
er fa
ctor
s. Es
sent
ially
all
men
with
circ
ulat
ing
andr
ogen
s will
dev
elop
mic
rosc
opic
pro
stat
e ca
ncer
if th
ey li
ve lo
ng e
noug
h.
Thur
sfiel
d et
al.,
(201
0)A
ustra
liaEp
idem
iolo
gica
l Rep
ort o
n ca
ncer
in
cide
nce
in V
icto
ria in
200
8SR
stan
dard
rate
13.
5A
ge S
tand
ard
rate
128
.7A
dig
est o
f fac
ts a
nd fi
gure
s on
canc
er in
Vic
toria
, Aus
tralia
in 2
008.
Age
gro
up b
y ge
nder
of c
ance
r inc
iden
ce is
giv
en a
s a
sum
mar
y ta
ble.
Pro
stat
e ca
ncer
has
the
lead
ing
canc
er in
cide
nce
in m
ales
.
Thur
sfiel
d et
al.,
(201
1)
Aus
tralia
Epid
emio
logi
cal R
epor
t on
soci
al
cont
ext o
f can
cer i
n V
icto
ria fo
r 201
0M
edia
n ag
e at
dia
gnos
is=6
7yea
rs
(a d
ecre
ase
in se
ven
year
s in
a de
cade
).Th
e m
edia
n ag
e at
dea
th=8
2 (7
8 in
199
0).
Dia
gnos
ed 1
in 7
Vic
toria
n M
en A
ged
75ye
ars
Fact
shee
ts o
f the
soci
al d
river
s and
rece
nt tr
ends
for t
he to
p fiv
e m
ost c
omm
on c
ance
rs a
nd c
ervi
cal c
ance
r in
2008
. The
se
incl
ude
the
agei
ng p
opul
atio
n, e
arly
det
ectio
n, a
nd g
ende
r diff
eren
ces.
Partn
er p
ublic
atio
n to
pre
viou
s pub
licat
ion.
Thur
sfiel
d &
Far
rugi
a, (2
011)
Aus
tralia
Epid
emio
logi
cal R
epor
t on
canc
er
stat
istic
s and
tren
ds in
Vic
toria
for 2
010
Inci
denc
e R
ate=
115.
4/Su
rviv
al R
ate=
13.3
Stea
dy in
crea
se in
surv
ival
ove
r the
last
20
year
s.A
dig
est o
f fac
ts a
nd fi
gure
s on
canc
er in
Vic
toria
, Aus
tralia
in 2
010.
Age
gro
up b
y ge
nder
of c
ance
r inc
iden
ce su
mm
ary
tabl
e an
d tre
nds i
n su
rviv
al.
Thur
sfiel
d et
al.,
(201
2)
Aus
tralia
Epid
emio
logi
cal R
epor
t on
estim
ates
of
surv
ival
in V
icto
ria5
year
surv
ival
(%) P
Ca=
91%
Rat
e of
dea
th=1
3.3/
Inci
denc
e R
ate=
115.
4D
escr
iptiv
e in
form
atio
n re
gard
ing
surv
ival
pat
tern
s for
Vic
toria
ns w
ith c
ance
r in
2006
-201
0. P
rogn
ostic
info
rmat
ion
rela
ting
to st
agin
g fo
r PC
a is
thro
ugh
the
asce
rtain
men
t of G
lees
on S
core
s.
Risk
-fact
or S
tudi
es
Stud
yC
ount
ryC
ases
(N)
Con
trol
s(N
)Fi
ndin
gs/O
R (9
5%C
I)Su
mm
ary
Lum
ey e
t al.,
(199
8)
USA
699
2,04
1A
ny O
R=1
.2 (9
5%C
I=0.
9–1.
5)A
lcoh
ol u
se a
nd p
rost
ate
canc
er in
U.S
. whi
tes a
dmitt
ed b
etw
een1
977
– 19
91. N
o as
soci
atio
n w
as se
en b
etw
een
pros
tate
can
cer a
nd
alco
hol i
ntak
e co
mpa
ring
ever
, cur
rent
and
form
er to
nev
er d
rinke
rs, n
ot e
ven
for t
he h
ighe
st re
porte
d le
vel o
f alc
ohol
con
sum
ptio
n.
Cui
et a
l., (2
001)
Aus
tralia
1476
1409
Pene
tranc
e to
80y
rs w
as th
e D
omin
ant e
ffect
~70%
(9
5% C
I 57-
85%
)R
eces
sive
and
X li
nked
~ 1
00%
Segr
egat
ion
anal
ysis
aim
ing
to d
etec
t gen
etic
fact
ors o
f 1,4
76 p
opul
atio
n-ba
sed
Aus
tralia
n fa
mili
es a
ffect
ed b
y pr
osta
te c
ance
r at a
ge
less
than
70y
ears
; acc
esse
d th
roug
h po
pula
tion
regi
strie
s in
Mel
bour
ne, S
ydne
y an
d Pe
rth. A
ppro
xim
atel
y 1/
30 (9
5% C
I 1/8
0-1/
12) m
en
wou
ld c
arry
the
dom
inan
t ris
k, a
nd 1
/140
(95%
CI 1
/220
-1/9
0) w
ould
car
ry th
e re
cess
ive
risk
or 1
/200
(95%
CI 1
/380
-1/1
00) w
ould
ca
rry
risk,
and
1/1
40 (9
5% C
I 1/2
20-1
/90)
wou
ld c
arry
the
X-li
nked
risk
.
Gile
s et a
l., (2
001)
Aus
tralia
1498
1434
Form
er S
mok
ers/
Cur
rent
Sm
oker
s:
1.02
(0.8
5-1.
22)/0
.82
(0.6
5-1.
05)
Mod
erat
e gr
ade
tum
ours
: 0.9
5 (0
.78-
1.15
)/0.7
6 (0
.59-
0.99
)H
igh-
grad
e tu
mou
rs: 1
.28
(0.9
6-1.
70)/1
.00
(0.6
7-1.
47)
An
Aus
tralia
n ca
se-c
ontro
l stu
dy th
at e
xam
ines
the
risk
of sm
okin
g an
d m
oder
ate
and
high
gra
de p
rost
ate
canc
er. T
here
was
no
evid
ence
of
a d
ose-
resp
onse
effe
ct fo
r dur
atio
n of
smok
ing,
am
ount
smok
ed, p
ack-
year
s of s
mok
ing
and
year
s sin
ce q
uitti
ng; a
nd m
ost O
R’s
at t
he
95%
con
fiden
ce in
terv
al fo
r the
se v
aria
bles
wer
e cl
ose
to u
nity
. It w
as c
oncl
uded
that
smok
ing
was
not
ass
ocia
ted
with
the
inci
denc
e of
pr
osta
te c
ance
r.
Gile
s et a
l., (2
003)
A
ustra
lia14
7614
09H
avin
g a
grow
th sp
urt l
ater
than
frie
nds r
educ
ed ri
sk (o
dds
ratio
[OR
] 0.7
9 [0
.63-
0.97
]) a
nd so
me
mea
sure
s of a
cne
also
ga
ve o
dds r
atio
s les
s tha
n 1,
for e
xam
ple,
hav
ing
faci
al a
cne
scar
ring
gave
an
OR
of 0
.67
(0.4
5-1.
00).
Inve
stig
atio
n of
ass
ocia
tions
bet
wee
n pr
osta
te c
ance
r ris
k an
d a
num
ber o
f mar
kers
of b
ody
grow
th, s
ize
and
chan
ges t
o si
ze in
a
popu
latio
n-ba
sed,
cas
e-co
ntro
l stu
dy in
Aus
tralia
from
199
4 to
199
8. A
naly
sis w
as p
erfo
rmed
on
all c
ases
and
als
o by
tum
our g
rade
. N
o as
soci
atio
ns w
ere
repo
rted
with
mea
sure
s of b
ody
size
incl
udin
g bo
dy m
ass i
ndex
and
lean
bod
y m
ass a
t age
21
or la
ter i
n ad
ult l
ife
Con
clud
ed th
at m
arke
rs o
f del
ayed
and
roge
n ac
tion,
such
as d
elay
ed g
row
th sp
urt i
n pu
berty
, and
mar
kers
of o
ther
and
roge
n-de
pend
ent
activ
ity in
pub
erty
, suc
h as
faci
al a
cne
scar
ring,
are
ass
ocia
ted
with
pro
stat
e ca
ncer
risk
but
no
asso
ciat
ions
with
mar
kers
of a
dult
body
si
ze a
nd g
row
th in
clud
ing
lean
bod
y m
ass c
ould
be
dete
cted
.
Dom
bi e
t al.,
(201
0)U
SA72
963
6G
reat
est r
isk
in U
SA: a
Bla
ck, m
arrie
d m
an, o
lder
than
60
year
s, w
ith a
t bes
t a h
igh
scho
ol d
iplo
ma
who
mad
e be
twee
n $2
5,00
0-$6
5,00
0
Inve
stig
ated
the
pote
ntia
l rel
atio
nshi
p be
twee
n oc
cupa
tion
hist
ory
and
pros
tate
can
cer r
isk
in a
pop
ulat
ion-
base
d ca
se–c
ontro
l stu
dy. T
he
varia
bles
incl
uded
: rac
e, a
ge g
roup
, sm
okin
g st
atus
, inc
ome,
mar
ital s
tatu
s, ed
ucat
ion
and
the
first
15
year
s of e
mpl
oym
ent h
isto
ry w
ere
exam
ined
by
sequ
entia
l odd
s rat
io a
naly
sis t
hen
com
pare
d to
a n
eura
l net
wor
k co
nsen
sus m
odel
. Thi
s wor
k su
ppor
ted
prev
ious
stud
ies
by fi
ndin
g w
ell k
now
n de
mog
raph
ic ri
sk fa
ctor
s for
pro
stat
e ca
ncer
incl
udin
g ce
rtain
pro
cess
ing
jobs
and
che
mic
al re
late
d jo
bs.
Whi
te e
t al.,
(201
1)U
SAC
ohor
t stu
dy87
,449
Bla
ck m
en: H
R, 1
.70
[95%
CI,
1.58
-1.8
3]
His
pani
c m
en: H
R, 1
.11
[95%
CI,
1.02
-1.2
0]bo
th m
en w
ere
mor
e lik
ely
to d
ie o
f pro
stat
e ca
ncer
com
pare
d w
ith w
hite
men
.
An
inve
stig
atio
n to
det
erm
ine
whe
ther
raci
al d
ispa
ritie
s in
surv
ival
for m
en d
iagn
osed
with
pro
stat
e ca
ncer
in T
exas
from
199
5 th
roug
h 20
02. T
he S
ES m
easu
re w
as b
ased
on
cens
us tr
act d
ata
refle
ctin
g m
edia
n ho
useh
old
inco
me,
med
ian
hom
e va
lue,
and
per
cent
ages
of
men
livi
ng b
elow
pov
erty
, with
a c
olle
ge e
duca
tion,
and
with
a m
anag
emen
t or p
rofe
ssio
nal o
ccup
atio
n. T
he p
atte
rn o
f sur
viva
l di
sadv
anta
ge fo
r bla
ck m
en h
eld
for t
hose
dia
gnos
ed w
ith lo
caliz
ed d
isea
se a
nd a
dvan
ced
dise
ase,
and
for t
hose
with
an
unkn
own
stag
e of
dis
ease
at d
iagn
osis
. Sub
stan
tial r
acia
l dis
parit
ies i
n pr
osta
te c
ance
r sur
viva
l wer
e re
porte
d fo
r men
in T
exas
.
Cro
ok e
t al.,
(201
2)C
anad
a69
0In
term
itten
t 69
6C
ontin
uous
Med
ian
Ove
rall
surv
ival
In
term
itten
t The
rapy
=8.8
yea
rs/C
ontin
uous
The
rapy
=9.1
yea
rsH
R=1
.02
at C
I at 9
5%:0
.86-
1.21
Ran
dom
ised
con
trol t
rial t
hat i
nves
tigat
ed in
term
itten
t and
roge
n de
priv
atio
n fo
r PSA
ele
vatio
n af
ter r
adio
ther
apy
wou
ld im
prov
e qu
ality
of
life
and
del
ay h
orm
one
resi
stan
ce. C
oncl
uded
that
inte
rmitt
ent a
ndro
gen
depr
ivat
ion
was
non
-infe
rior t
o co
ntin
uous
ther
apy
with
re
spec
t to
over
all s
urvi
val.
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014 503
DOI:http://dx.doi.org/10.7314/APJCP.2014.15.2.501An Update on Occupation and Prostate Cancer
several U.S. authors have identified racial disparities for Black men (Dombi et al., 2010) with a hazard Ratio of 1.70 (95%CI 1.58-1.83) (White et al., 2011). Literature Review
In this update, we review in narrative form the literature between 2000 and 2012, dividing occupational risk factors into four groups: chemicals and heavy (and toxic) metals (Klaassen et al., 1996), ergonomic, physical, environmental and psychosocial factors. We reviewed a number of systematic reviews and believe they are of good strength and quality of evidence and have added subsequent articles not covered in the reviews. The following key words and phrases were used in an online literature search of the PubMed Medline (NLM) and Medline 1996-present databases at OVID database links. Alcohol, aliphatic, alicyclic and aromatic hydrocarbon solvents, andrology, arsenic, cadmium, diet, environmental factors, ergonomic, fungicides herbicides and insecticides, heat, incidence, inconvenient & difficult work postures, ionizing radiation, lead, low frequency magnetic fields (EMF), manual handling of burdens, maximum allowable concentrations, mortality, nickel, occupational exposure, organic solvents and chlorinated hydrocarbon solvents, physical workloads, physical factors, prevalence, prevention, prostate cancer, prostate neoplasms, psychosocial factors, radiation exposure, radio frequency radiation (RFR), risk factors, risk, sedentary work, smoking, standing work, threshold, toxic metals, ultraviolet radiation and workload. Articles published between 2000 and 2012 were reviewed and selected on the basis of their adherence to review methodology were included in this update. The reviews which have been evaluated on the strength of their methodology are listed separately to the new studies and both groups are presented in chronological order in the tables to illustrate the order and knowledge progression in which this research has been undertaken.
Heavy and toxic metals The main chemical risk factors within this category include aliphatic and alicyclic hydrocarbon solvents, aromatic hydrocarbon solvents, chlorinated hydrocarbon solvents, other organic solvents, arsenic, cadmium, chromium, lead, nickel, fungicides, herbicides and insecticides. Past reviews have separately discussed individual elements within this category. Table 2A lists important reviews (7 in-total) and Table 2B studies (14 in-total) related to heavy metals. An early review by Wong and Raabe (2000), which was confined to lead exposure related to petroleum workers, reported no association. Another investigation (Siddiqui et al., 2002) from India, concluded that environmental exposure of ageing males to lead might be a risk factor, but more recent studies by Lam et al. (2007) and Gwini et al. (2012) reported that lead was not associated with prostate cancer. Overall, the evidence pertaining to lead is inconsistent and it is unlikely occupational exposure to lead is associated with prostate cancer incidence. A recent review of arsenic exposure by Benbrahim-
Tallae and Waalks (2008) suggested there was clear in vitro evidence of arsenic precipitating events leading to androgen independence during prostate cancer cell progression. However, the authors suggest there is essentially no available information on arsenic levels in the human prostatic tissue and urged that further work in this area was required. Arsenic is a major risk factor for Blackfoot Disease (BFD), a unique peripheral vascular disease that was endemic to the south-western coast of Taiwan. A Taiwanese study (Yang et al., 2008) of BFD, arsenic exposure and prostate cancer investigated the tap-water supply system before and after replacing the use of an artesian well water source for drinking and cooking in the early 1960s. The objective of this study was to determine whether prostate cancer mortality decreased after the improvement of the drinking-water supply system by eliminating arsenic ingestion from the artesian well water. Standardized mortality ratios (SMRs) for prostate cancer were calculated for the BFD endemic area for the years 1971-2006. Results showed that mortality attributed to prostate cancer declined gradually after the improvement of the drinking-water supply system. The authors claimed a direct cause and effect relationship associated with arsenic exposure. With respect to cadmium exposure Koyama et al. (2002) reported in a review that cadmium increases the occurrences of tumours in testis, lung, prostatic, haematopoietic tissues and injection sites. It was recently restated by the IARC that in view of positive associations observed between cadmium and cadmium compounds and cancer of the prostate, cadmium and cadmium compounds are carcinogenic to humans, and therefore are classed as Group 1 (IARC working group, 2012). Cadmium exposure is occupationally associated with nickel-cadmium battery manufacture and cadmium recovery plant smelting and is also associated with cigarette smoking; but has not been associated with prostate cancer in this instance. Verougstraete et al. (2003) in the latest available update of their systematic review did not confirm an association between cadmium exposure and prostate cancer and concluded that environmentally exposed populations were not at an increased relative risk of prostate cancer. In 2001, Achanzar et al. (2001) investigated the intensity of exposure to a range of hazardous chemicals including cadmium and a year later Achanzar et al. (2002) investigated acquired apoptotic resistance in cadmium-transformed human prostate epithelial cells (CPTE). They hypothesized that acquired apoptotic resistance might be a key aspect of cadmium-induced malignant transformation of prostate epithelial cells and could contribute to both tumour initiation and the acquisition of aggressive characteristics subsequent to tumour formation. However, other researchers (Singh et al., 2012) have identified this self destructive cell (apoptotic) process as the key to finding a method of destroying prostate cancer cells. In a later review of laboratory rodent studies, Waalkes (2003) described cadmium as a heavy metal of considerable environmental and occupational concern. Waalkes concluded that cadmium could cause a number of molecular lesions that would be relevant to oncogenesis
Glenn Doolan et al
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014504
in various cellular model systems. However, other investigations indicate cadmium to be poorly mutagenic and probably acting through indirect or epigenetic mechanisms, potentially including aberrant activation of oncogenes and suppression of apoptosis. A later review (Goyer et al., 2004) concluded that suppression of DNA repair added to the population of cells with damaged DNA and chemical-induced apoptosis could be blocked by cadmium, facilitating aberrant cell accumulation. These hypotheses gained further support (Achanzar et al., 2002; Nakamura et al., 2002; Platz et al., 2002; Vinceti et al., 2007) following investigations by Platz et al. (2002) and Nakamura et al. (2002). Further investigations have suggested that a combination of lead and cadmium may initiate the development of prostate cancer due to their combined effect on testosterone (Telisman et al., 2007). In contrast to the earlier findings, Huff et al. (2007), Van Wijngaarden et al. (2008) and Li et al. (2011) failed to implicate cadmium in prostate carcinogenesis. Although Li et al. (2011) did suggest there was a dose response relationship with carcinogenesis at other organs. Other studies have examined the zinc: cadmium ratios (Drasch et al., 2005, Anetor et al., 2008) and the possibility that reduced selenium uptakes may have a more pronounced effect in the presence of high cadmium levels. Lee et al. (2009) proposed that a cysteine-rich protein called metallothionein (MT) binds heavy metals (such as cadmium) and would, thus, protect against prostate cancer. Sahmoun et al. (2005) in a review of 15 studies concluded that in contrast to laboratory studies, epidemiological studies do not convincingly implicate cadmium as a cause of prostate cancer and suggested that incorporating biological measures of cadmium exposure in epidemiological studies might remove this discrepancy. A further metal of interest that may be associated with prostate cancer is hexavalent chromium, which has been classified as an IARC group 1 carcinogen since the 1980s. Trivalent chromium compounds are not considered carcinogenic and are necessary for sugar and lipid metabolism. In the review update period we found no reviews or studies addressing chromium compounds and prostate cancer.
Chemical exposures A number of other miscellaneous occupational chemical exposures have been investigated in regard to prostate cancer risk. See Table 3A and 3B for summaries on occupational chemical exposure. For example, Ruder et al. (2004) investigated mortality rates Ta
ble
2A. T
oxic
Met
als R
evie
ws
Rev
iew
Cou
ntry
Met
hod
Find
ings
OR
(95%
CI)
Sum
mar
y
Won
g &
Raa
be, (
2000
)M
ainl
y U
SA.
Rev
iew
and
met
a-an
alys
is o
f 350
,000
pe
trole
um w
orke
rs
Sum
mar
y: S
MR
=0.9
8% (C
I 0.9
4-1.
03)
Lim
itatio
n: N
o le
ngth
of e
mpl
oym
ent
In a
dditi
on to
the
qual
itativ
e re
view
of i
ndiv
idua
l stu
dies
, a m
eta-
anal
ysis
was
per
form
ed to
com
bine
dat
a fr
om in
divi
dual
coh
ort s
tudi
es o
f pet
role
um w
orke
rs. E
leva
ted
mor
talit
y fr
om p
rost
ate
canc
er w
as n
oted
in sh
ort-t
erm
wor
kers
at a
U.S
. refi
nery
and
in sh
ort-t
erm
wor
kers
em
ploy
ed in
cer
tain
cra
fts a
t U.S
. cru
de o
il op
erat
ions
. How
ever
, th
e ab
senc
e of
an
upw
ard
trend
by
leng
th o
f em
ploy
men
t in
thes
e w
orke
rs a
rgue
d ag
ains
t an
asso
ciat
ion
betw
een
expo
sure
to p
etro
leum
pro
duct
s and
pro
stat
e ca
ncer
. For
all
petro
leum
wor
kers
as a
who
le, m
orta
lity
from
pro
stat
e ca
ncer
was
as e
xpec
ted.
Koy
ama
et a
l., (2
002)
Japa
nLa
bora
tory
Rev
iew
Car
cino
geni
city
test
s sho
wed
that
exp
osur
e to
Cd
incr
ease
d th
e oc
curr
ence
of t
umou
rs in
test
is, l
ung,
pro
s-ta
te, h
emat
opoi
etic
tiss
ues,
and
inje
ctio
n si
tes.
Stud
ies w
ere
revi
ewed
on
geno
toxi
city
and
car
cino
geni
city
of c
adm
ium
(Cd)
. Sal
mon
ella
typh
imur
ium
and
Esc
heric
hia
coli
expo
sed
to C
adm
ium
(Cd)
did
not
show
mut
a-ge
nici
ty, w
here
as c
ultu
red
mam
mal
ian
cells
exp
osed
to C
d sh
owed
mut
atio
n, D
NA
stra
nd b
reak
s, an
d ch
rom
osom
al a
berr
atio
ns. A
ll av
aila
ble
data
sugg
est t
hat C
d sh
ould
be
reas
sign
ed to
IAR
C G
roup
2A
(pro
babl
y ca
rcin
ogen
ic to
hum
ans)
from
the
curr
ent G
roup
1.
Vero
ugst
raet
e et
al.,
(200
3)B
elgi
umSy
stem
atic
revi
ewSM
R <
130
Cd
OR
=1.7
(95%
CI:
1.0-
3.1)
SMR
99-
75 C
d (1
943
- 89)
The
asso
ciat
ion
betw
een
cadm
ium
exp
osur
e an
d pr
osta
te c
ance
r was
not
con
firm
ed in
the
late
st a
vaila
ble
upda
tes.
Stud
ies i
n en
viro
nmen
tally
exp
osed
pop
ulat
ions
do
not
indi
cate
an
incr
ease
d re
lativ
e ris
k of
pro
stat
e ca
ncer
.
Wal
kes,
(200
3)U
SA a
nd H
olla
ndLa
bora
tory
Rev
iew
Cad
miu
m c
ould
pot
entia
lly a
ffect
all
the
vario
us st
ages
of
the
Car
cino
geni
c Pr
oces
s, in
clud
ing
initi
atio
n, p
rese
n-ta
tion
and
prog
ress
ion.
Cad
miu
m e
xpos
ure
has b
een
linke
d to
hum
an p
rost
ate
canc
er. M
ost s
tudi
es in
dica
te c
adm
ium
is p
oorly
mut
agen
ic a
nd p
roba
bly
acts
thro
ugh
indi
rect
or e
pige
netic
mec
hani
sms,
pote
ntia
lly in
clud
ing
aber
rant
act
ivat
ion
of o
ncog
enes
and
supp
ress
ion
of a
popt
osis
.
Goy
er e
t al.,
(200
4)U
SA a
nd H
olla
ndR
evie
w29
arti
cles
Zinc
defi
cien
cy d
epre
sses
cad
miu
m in
duce
d pr
osta
te
canc
er se
cond
ary
to te
stic
ular
toxi
city
. Red
uctio
n in
se
cret
ion
of te
stos
tero
ne.
Cad
miu
m a
nd c
adm
ium
com
poun
ds a
re k
now
n to
be
hum
an c
arci
noge
ns b
ased
on
findi
ngs o
f inc
reas
ed ri
sk to
lung
can
cer a
mon
g ex
pose
d w
orke
rs, b
ut a
rela
tions
hip
betw
een
canc
er o
f the
pro
stat
e an
d/or
test
is in
hum
ans i
s unc
lear
. The
pat
hoge
nesi
s of p
rost
atic
cad
miu
m c
arci
noge
nesi
s mig
ht in
clud
e ab
erra
nt g
ene
expr
essi
on re
sulti
ng in
stim
ulat
ion
of c
ell p
rolif
erat
ion
or b
lock
age
of a
popt
osis
. Act
ivat
ion
of tr
ansc
riptio
n fa
ctor
s suc
h as
the
met
allo
thio
nein
gen
e an
d ac
tivat
ion
of so
me
prot
o-on
coge
nes m
ay e
nhan
ce c
ell
prol
ifera
tion
with
dam
aged
DN
A. S
uppr
essi
on o
f DN
A re
pair
wou
ld a
dd to
the
popu
latio
n of
cel
ls w
ith d
amag
ed D
NA
. Che
mic
ally
indu
ced
apop
tosi
s can
be
bloc
ked
by
cadm
ium
, fac
ilita
ting
aber
rant
cel
l acc
umul
atio
n.
Sahm
ourn
et a
l., (2
005)
USA
3 de
scrip
tive
stud
ies (
75%
) rep
orte
d a
posi
tive
asso
ciat
ion
betw
een
cadm
ium
and
pr
osta
te c
ance
r.5
case
-con
trols
(50%
) rep
orte
d a
posi
tive
asso
ciat
ion.
3 co
horts
(33%
) rep
orte
d a
posi
tive
asso
ciat
ion.
4 co
horts
exp
osed
in o
ccup
atio
nal n
icke
l-cad
miu
m b
atte
ries S
MR
s was
wea
kly
but
not s
igni
fican
tly p
ositi
ve: 1
26 (9
5%C
.I.: 8
3-18
4).
This
arti
cle
revi
ews t
he e
pide
mio
logi
cal l
itera
ture
on
cadm
ium
and
pro
stat
e ca
ncer
with
a sp
ecia
l foc
us o
n hi
ghly
exp
osed
occ
upat
iona
l coh
orts
bet
wee
n 19
66 a
nd 2
002.
All
publ
ishe
d an
alyt
ical
and
des
crip
tive
stud
ies t
hat i
nclu
ded
rele
vant
dat
a w
ere
revi
ewed
in a
dditi
on to
the
expe
rienc
e of
coh
orts
hig
hly
expo
sed
to c
adm
ium
in n
icke
l-cad
miu
m
batte
ry p
lant
s. In
con
trast
to la
bora
tory
stud
ies,
epid
emio
logi
cal s
tudi
es d
o no
t con
vinc
ingl
y im
plic
ate
cadm
ium
as a
cau
se o
f pro
stat
e ca
ncer
. Fut
ure
epid
emio
logi
cal s
tudi
es
that
atte
mpt
to re
solv
e th
e di
scre
panc
y be
twee
n la
bora
tory
and
epi
dem
iolo
gica
l stu
dies
of c
adm
ium
car
cino
gene
sis m
ay b
enefi
t fro
m in
corp
orat
ing
biol
ogic
al m
easu
res o
f ca
dmiu
m e
xpos
ure.
Huf
f et a
l., (2
007)
USA
Rev
iew
The
basi
c m
etal
cat
ioni
c po
rtion
of c
adm
ium
is
resp
onsi
ble
for b
oth
toxi
c an
d ca
rcin
ogen
ic a
ctiv
ity,
and
the
mec
hani
sm o
f car
cino
geni
city
app
ears
to b
e m
ulti-
fact
oria
l.
Avai
labl
e in
form
atio
n ab
out t
he c
arci
noge
nici
ty o
f cad
miu
m a
nd c
adm
ium
com
poun
ds is
revi
ewed
, eva
luat
ed, a
nd d
iscu
ssed
. Cad
miu
m a
nd c
adm
ium
com
poun
ds h
ave
been
cl
assi
fied
as k
now
n hu
man
car
cino
gens
by
the
Inte
rnat
iona
l Age
ncy
for R
esea
rch
on C
ance
r and
the
Nat
iona
l Tox
icol
ogy
Prog
ram
bas
ed o
n ep
idem
iolo
gic
stud
ies s
how
ing
a ca
usal
ass
ocia
tion
with
pro
stat
e ca
ncer
, and
stud
ies i
n ex
perim
enta
l ani
mal
s, de
mon
stra
ting
that
cad
miu
m c
ause
s tum
ours
at m
ultip
le ti
ssue
site
s, by
var
ious
rout
es o
f exp
osur
e,
and
in se
vera
l spe
cies
and
stra
ins.
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014 505
DOI:http://dx.doi.org/10.7314/APJCP.2014.15.2.501An Update on Occupation and Prostate Cancer
Tabl
e 2B
. Tox
ic M
etal
s Stu
dies
Stud
yC
ount
ryC
ases
(N
)C
ontr
ols
(N)
Find
ings
OR
(95%
CI)
Sum
mar
y
Shar
ma
Wag
ner e
t al.,
(2
000)
Swed
en
36,2
69A
gric
ultu
re: S
IR 1
.05
95%
CI 1
.03-
1.08
farm
ers:
SIR
1.0
7 95
% C
I 1.0
4-1.
10so
ap a
nd p
erfu
me
man
ufac
ture
,SI
R 1
.46
95%
CI 1
.10-
1.89
leat
her p
roce
ssin
g: S
IR 1
.18
95%
CI 1
.00-
1.48
Occ
upat
ion
and
pros
tate
can
cer r
isk
in S
wed
en. L
inke
d pr
osta
te c
ance
r cas
es re
porte
d to
the
Swed
ish
Nat
iona
l Can
cer R
egis
try d
urin
g 19
61 to
197
9 w
ith e
mpl
oym
ent i
nfor
mat
ion
from
the
1960
Nat
iona
l Cen
sus.
Stan
dard
ized
inci
denc
e ra
tios f
or p
rost
ate
canc
er, w
ithin
maj
or (1
-dig
it), g
ener
al (2
-dig
it), a
nd sp
ecifi
c (3
-dig
it) in
dust
ries a
nd o
ccup
atio
ns, w
ere
calc
ulat
ed. S
igni
fican
t exc
ess r
isks
wer
e se
en fo
r agr
icul
ture
-rel
ated
indu
strie
s, so
ap a
nd p
erfu
me
man
ufac
ture
, and
leat
her p
roce
ssin
g in
dust
ries.
Sign
ifica
ntly
ele
vate
d st
anda
rdiz
ed
inci
denc
e ra
tios w
ere
also
seen
for t
he fo
llow
ing
occu
patio
ns: f
arm
ers,
leat
her w
orke
rs, a
nd w
hite
-col
lar o
ccup
atio
ns. T
he re
sults
sugg
este
d th
at fa
rmer
s, ce
rtain
occ
upat
ions
and
in
dust
ries w
ith e
xpos
ures
to c
adm
ium
, her
bici
des,
and
ferti
lizer
s and
men
with
low
occ
upat
iona
l phy
sica
l act
ivity
leve
ls h
ave
elev
ated
pro
stat
e ca
ncer
risk
s.
Ach
anza
r et a
l.,
(200
1)U
SA
Labo
rato
ryIn
vest
igat
ion
Mal
igna
nt tr
ansf
orm
atio
n of
the
non-
tum
ourig
enic
hum
an
pros
tatic
epi
thel
ial c
ell l
ine
RWPE
-1 b
y in
vitr
o ca
dmiu
m
expo
sure
.
The
cadm
ium
-tran
sfor
med
cel
ls e
xhib
ited
a lo
ss o
f con
tact
inhi
bitio
n in
vitr
o an
d ra
pidl
y fo
rmed
hig
hly
inva
sive
and
occ
asio
nally
met
asta
tic a
deno
-car
cino
mas
upo
n in
ocul
atio
n in
to m
ice.
The
tran
sfor
med
cel
ls a
lso
show
ed in
crea
sed
secr
etio
n of
MM
P-2
and
MM
P-9,
a p
heno
men
on o
bser
ved
in h
uman
pro
stat
e tu
mou
rs a
nd li
nked
to a
ggre
ssiv
e be
havi
our.
Cad
miu
m-in
duce
d m
alig
nant
tran
sfor
mat
ion
of h
uman
pro
stat
e ep
ithel
ial c
ells
stro
ngly
forti
fies t
he e
vide
nce
for a
pot
entia
l rol
e of
cad
miu
m in
pro
stat
e ca
ncer
.
Plat
z et
al.,
(200
2)U
SA11
522
7O
R=4
59/5
4.5p
pmO
R=1
55/1
64pp
mA
ge m
atch
ed c
ontro
ls. T
oena
il sa
mpl
es te
sted
. Sup
ports
the
hypo
thes
is th
at c
adm
ium
exp
osur
e in
crea
ses P
Ca.
in th
e pr
esen
ce o
f a lo
w z
inc
inta
ke.
Nak
amur
a et
al.,
(2
002)
USA
Labo
rato
ryIn
vest
igat
ion
Tum
ours
cha
ract
eriz
ed h
isto
logi
cally
as p
oorly
-diff
eren
ti-at
ed a
deno
carc
inom
as, e
xpre
ssin
g pr
osta
te-s
peci
fic a
ntig
en
(PSA
), an
drog
en re
cept
or (A
R),
pros
tate
stem
cel
l ant
igen
(P
SCA
), N
KX
3.1
and
cyto
kera
tin 8
(CK
8).
Epid
emio
logi
cal a
nd a
nim
al st
udie
s hav
e su
gges
ted
its c
arci
noge
nic
pote
ntia
l on
the
pros
tate
. Non
-tum
ourig
enic
hum
an p
rost
ate
epith
elia
l cel
ls (p
RN
S-1-
1) im
mor
taliz
ed b
y si
mia
n pa
pova
viru
s (SV
40) w
ere
trans
form
ed a
fter r
epea
ted
expo
sure
s to
cadm
ium
. Suc
h tra
nsfo
rman
ts sh
owed
mor
phol
ogic
al a
ltera
tions
, anc
hora
ge-in
depe
nden
t gro
wth
in so
ft ag
ar, a
nd
form
ed tu
mou
rs w
hen
trans
plan
ted
into
SC
ID m
ice
Thes
e fin
ding
s pro
vide
evi
denc
e of
mal
igna
nt tr
ansf
orm
atio
n of
hum
an p
rost
ate
epith
elia
l cel
ls e
xpos
ed to
this
env
ironm
enta
lly
impo
rtant
che
mic
al.
Sidd
ique
et a
l.,
(200
2)In
dia
xx
Pros
tate
(r =
0.7
7, P
< 0
.05)
B
PH (r
= 0
.32,
P <
0.0
5) a
nd
norm
al (r
= 0
.30,
P <
0.0
5).
Eval
uatin
g th
e po
ssib
le ro
le o
f env
ironm
enta
l exp
osur
e to
lead
as a
risk
fact
or fo
r pro
stat
e pa
thol
ogy
in p
atie
nts s
uffe
ring
from
pro
stat
e ca
ncer
and
ben
ign
pros
tate
hyp
erpl
asia
. B
Pb w
as si
gnifi
cant
ly h
ighe
r in
PCA
and
BPH
cas
es th
an u
sual
. Blo
od le
vels
of z
inc
and
copp
er w
ere
sign
ifica
ntly
low
er in
PC
A a
nd B
PH c
ases
whe
n co
mpa
red
with
con
trols
. H
owev
er, p
ositi
ve a
ssoc
iatio
n be
twee
n bl
ood
lead
and
TB
AR
S w
as re
lativ
ely
high
er in
PC
A p
atie
nts t
han
in B
PH a
nd n
orm
al. T
hese
resu
lts se
em to
sugg
est f
or th
e fir
st ti
me
that
en
viro
nmen
tal e
xpos
ure
of a
ging
mal
es to
lead
may
be
a ris
k fa
ctor
for p
rost
ate
canc
er a
nd/o
r ben
ign
pros
tate
hyp
erpl
asia
pos
sibl
y th
roug
h ge
nera
tion
of re
activ
e ox
ygen
spec
ies
and/
or re
duci
ng th
e le
vel o
f zin
c w
hich
act
s as a
cel
lula
r gro
wth
pro
tect
or.
Ach
anza
r et a
l.,
(200
2)U
SA
Labo
rato
ryIn
vest
igat
ion
CTP
E ce
lls e
xhib
ited
incr
ease
d re
sist
ance
to a
popt
osis
in
duce
d by
cad
miu
m, c
ispl
atin
, and
eto
posi
de. C
TPE
cells
al
so e
xhib
ited
low
er c
aspa
se-3
act
ivity
vs.
RWPE
-1 a
fter
etop
osid
e tre
atm
ent.
Perf
orm
ed m
olec
ular
com
paris
ons b
etw
een
the
cadm
ium
-tran
sfor
med
pro
stat
e ep
ithel
ial c
ell l
ine
CTP
E an
d th
e no
ntum
orig
enic
par
enta
l lin
e RW
PE-1
. Rib
onuc
leas
e pr
otec
tion
assa
ys c
onfir
med
glo
bal d
own-
regu
latio
n of
cas
pase
gen
e ex
pres
sion
in C
TPE.
CTP
E ce
lls e
xhib
ited
alte
red
expr
essi
on o
f im
porta
nt a
popt
otic
regu
lato
rs a
s wel
l as r
esis
tanc
e to
se
vera
l apo
ptot
ic st
imul
i. It
was
hyp
othe
size
d th
at a
cqui
red
apop
totic
resi
stan
ce m
ay b
e a
key
aspe
ct o
f cad
miu
m-in
duce
d m
alig
nant
tran
sfor
mat
ion
of p
rost
ate
epith
elia
l cel
ls a
nd
that
this
may
con
tribu
te to
bot
h tu
mou
r ini
tiatio
n an
d th
e ac
quis
ition
of a
ggre
ssiv
e ch
arac
teris
tics s
ubse
quen
t to
tum
our f
orm
atio
n.
Dra
sch
et a
l.,
(200
5) U
SA12
9La
b.
Stud
yN
orm
al S
e:C
d 1:
1PC
a Se
:Cd
<1:1
A la
bora
tory
stud
y of
pro
stat
e gl
ands
from
dec
ease
d m
en b
etw
een
15-9
0yea
rs in
dica
ted
a lo
wer
risk
with
mod
erat
e to
hig
h zi
nc in
take
. The
exc
essi
ve a
ccum
ulat
ion
of C
adm
ium
in
the
pros
tate
s of s
mok
ers a
long
with
sub-
optim
al se
leni
um in
take
s cou
ld e
xpla
in w
hy sm
oker
s dev
elop
mor
e ag
gres
sive
and
leth
al fo
rms o
f pro
stat
e ca
ncer
than
non
smok
ers.
Vin
cent
i et a
l., (2
007)
Italy
4058
OR
3rd q
uarti
le 1
.3O
R 4
th q
uarti
le 4
.7 p
=0.0
04A
stud
y su
ppor
ting
Plat
z et
al.
(200
2) st
udy
on C
adm
ium
toe
nail
clip
ping
leve
ls. B
oth
supp
ort t
he h
ypot
hesi
s tha
t cad
miu
m e
xpos
ure
incr
ease
s PC
a.
Lam
et a
l., (2
007)
USA
8630
72C
ance
r SIR
0.5
1 (0
.41-
0.62
)C
aP S
IR 0
.35(
0.20
-0.5
7)U
SA st
udy
on o
ccup
atio
nal e
xpos
ure
to le
ad is
not
ass
ocia
ted
with
Can
cer.
Lim
itatio
ns: h
ealth
y w
orke
r effe
ct.
Telis
man
et a
l.,
(200
7) C
roat
ia24
0B
Pb M
edia
n 49
Mic
ro g
/LR
ange
: 11-
149
Mic
ro g
/LB
lood
Lea
d (B
Pb) l
evel
s wer
e as
certa
ined
. Res
ults
in li
ne w
ith g
ener
al p
opul
atio
ns w
orld
wid
e. T
he o
bser
ved
sign
ifica
nt sy
nerg
istic
effe
ct o
f BPb
and
BC
d in
itiat
es th
e de
velo
pmen
t of
PC
a be
caus
e te
stos
tero
ne a
ugm
ents
the
prog
ress
of P
Ca
in it
s ear
ly st
ages
.
Ben
brah
im-T
alla
a et
al
., (2
008)
USA
Clin
ical
Rep
ort
and
revi
ewIn
dica
tes m
ore
of a
n en
viro
nmen
tal p
robl
em th
an a
n oc
cupa
-tio
n ex
posu
re p
robl
em.
The
pros
tate
is a
targ
et fo
r ino
rgan
ic a
rsen
ic c
arci
noge
nesi
s. In
ter a
nd In
tra-r
acia
l diff
eren
ces p
rom
ote
pros
tate
can
cer i
ncid
ence
and
mor
talit
y ra
tes w
orld
-wid
e. F
ound
ry W
orke
rs
(Cop
per)
had
a h
ighe
r PSA
leve
l.
Yang
et a
l., (2
008)
Taiw
an79
Tim
e Se
ries
The
estim
ated
slop
e fo
r the
SM
R (
rate
of d
ecre
ase
per y
ear)
in
the
linea
r tim
e tre
nd a
naly
sis w
as –
5.3
3 an
d si
gnifi
cant
.Ta
iwan
stud
y (1
971-
2006
) whi
ch e
xam
ined
the
effe
cts o
f the
impr
ovem
ent i
n w
ater
supp
ly. M
orta
lity
from
PC
a de
clin
ed g
radu
ally
afte
r use
of c
lean
wat
er. T
his i
s see
n as
a c
ause
an
d ef
fect
resu
lt co
ncer
ning
Ars
enic
.
Ane
tor e
t al.,
(200
8)N
iger
ia55
41Zn
:CD
(p<0
.001
)St
udy
on to
bacc
o sm
oke
and
cadm
ium
. The
y hy
poth
esiz
e th
at in
crea
sed
Cad
miu
m: Z
inc
ratio
is a
pot
entia
l bio
mar
ker f
or P
Ca.
Van
Wijn
gaar
den
et
al.,
(200
8)U
SA
422
1,32
0A
n in
crea
se in
1 m
icro
g/g
cre
atin
ine
cadm
ium
exp
osur
e w
as
asso
ciat
ed w
ith a
35%
incr
ease
in P
SA le
vel.
2001
-200
2 N
atio
nal H
ealth
and
Nut
ritio
n Ex
amin
atio
n Su
rvey
(NH
AN
ES).
Littl
e ev
iden
ce fo
r an
asso
ciat
ion
betw
een
cadm
ium
and
ele
vate
d PS
A le
vel w
as o
bser
ved.
Zin
c is
pr
otec
tive
in c
adm
ium
exp
osur
e. W
hen
zinc
leve
ls d
eclin
e PS
A le
vels
incr
ease
d w
hen
cadm
ium
leve
ls re
mai
ned
high
.
Lee
et a
l., (2
009)
Taiw
an18
35M
T ex
pres
sion
in p
atie
nts w
ith B
PH w
as 3
.4-f
old
high
er
than
in th
ose
with
CaP
Cys
tein
e-ric
h pr
otei
n ca
lled
met
allo
thio
nein
(MT)
whi
ch b
inds
hea
vy m
etal
s and
is p
rote
ctiv
e fo
r PC
a. A
dditi
onal
stud
ies a
re n
eede
d to
reve
al th
e fa
ctor
s tha
t infl
uenc
e th
e ex
pres
-si
on o
f MT
in p
rost
ate
epith
elia
l cel
ls, a
nd to
ana
lyze
the
free
and
com
poun
d fo
rms o
f Cd
at th
e sa
me
time.
Sing
h et
al.,
(201
2)In
dia
Labo
rato
ryIn
vest
igat
ion
Prot
ectio
n of
N-a
cety
l cys
tein
e (N
AC
) aga
inst
RO
S cl
early
su
gges
ted
the
impl
icat
ion
of R
OS
in h
yper
-act
ivat
ion
of
apop
tosi
s and
cel
l dea
th.
This
stud
y w
as d
esig
ned
to in
vest
igat
e th
e po
ssib
le m
echa
nism
s of a
popt
osis
indu
ced
by b
iosu
rfac
tant
stab
ilize
d C
dS Q
Ds (
deno
ted
as “
bsC
dS Q
Ds”
) in
hum
an p
rost
ate
canc
er
LNC
aP c
ells
. The
aut
hors
con
clud
e th
at b
iolo
gica
lly st
abili
zed
CdS
QD
s bea
r the
pot
entia
l of i
ts a
pplic
atio
ns in
bio
med
icin
e, su
ch a
s tum
our t
hera
py sp
ecifi
cally
by
indu
cing
ca
spas
e-de
pend
ent a
popt
otic
cel
l dea
th o
f hum
an p
rost
ate
canc
er L
NC
aP c
ells
.
Li Q
uian
et a
l.,
(201
1)C
hina
1403
Men
Com
pare
d w
ith u
rinar
y C
d <3
.0 μ
g/g
Cr g
roup
, the
HR
of
5.0–
9.9
μg/g
Cr a
nd ≥
10.0
μg/
g C
r gro
ups w
ere
sign
ifica
ntly
in
crea
sed
afte
r adj
ustm
ent f
or a
ge in
bot
h se
xes:
1.2
4 (9
5%
CI 1
.01–
1.51
) and
1.4
8 (9
5% C
I 1.1
7–1.
90) f
or m
en; T
he
mos
t fre
quen
t cau
se o
f dea
th w
as m
alig
nant
neo
plas
m in
m
en.
This
stud
y ai
med
to a
sses
s the
influ
ence
of e
nviro
nmen
tal e
xpos
ure
to C
d on
long
term
out
com
e of
inha
bita
nts l
ivin
g in
an
area
pol
lute
d by
Cd.
. The
subj
ects
wer
e di
vide
d in
to 4
gr
oups
acc
ordi
ng to
the
amou
nt o
f urin
ary
Cd
leve
l (<3
.0 μ
g/g
crea
tinin
e (C
r), 3
.0–4
.9 μ
g/g
Cr,
5.0–
9.9
μg/g
Cr,
and
≥10.
0 μg
/g C
r). M
orta
lity
was
cal
cula
ted
by th
e pe
rson
-yea
rs
met
hod.
Haz
ards
ratio
s (H
R) a
nd 9
5% c
onfid
ence
inte
rval
s (C
I) w
ere
asse
ssed
by
the
Cox
’s p
ropo
rtion
al h
azar
d m
odel
. The
se re
sults
sugg
est a
dos
e-re
spon
se re
latio
nshi
p be
twee
n C
d bo
dy b
urde
n an
d m
orta
lity
for c
ardi
ovas
cula
r dis
ease
s, ce
rebr
o-va
scul
ar d
isea
ses a
nd n
ephr
itis a
nd n
ephr
osis
. The
sam
ple
size
for P
rost
ate
canc
er w
as n
=3 a
nd w
as n
ot si
gnifi
-ca
nt.
Gw
ini e
t al.,
(201
2)A
ustra
lia40
641
14O
vera
ll de
ath
SMR
= 11
1; 9
5% C
I, =1
01-1
23 G
I dea
ths
SMR
= 16
7; 9
5% C
I= 1
10-2
50de
aths
from
SM
R=
135;
95%
CI=
105
-174
exte
rnal
cau
ses
This
coh
ort s
tudy
mea
sure
s mor
talit
y an
d ca
ncer
inci
denc
e in
a c
ohor
t of l
ead-
expo
sed
wor
kers
by
usin
g bl
ood
lead
leve
ls to
ass
ess e
xpos
ure.
Sub
ject
s wer
e m
atch
ed to
can
cer a
nd
deat
h re
gist
ries.
Obs
erve
d de
ath
and
canc
er in
cide
nce
rate
s wer
e co
mpa
red
with
pop
ulat
ion
rate
s to
obta
in st
anda
rdiz
ed m
orta
lity
ratio
s (SM
R) a
nd st
anda
rdiz
ed in
cide
nce
ratio
s (S
IR).
Ove
rall
mor
talit
y w
as e
leva
ted.
Alth
ough
inci
denc
e ra
tes o
f ove
rall
canc
er w
ere
low,
furth
er st
udie
s and
ana
lysi
s are
requ
ired
to in
vest
igat
e an
y bi
olog
ical
ly p
laus
ible
ass
ocia
-tio
ns b
etw
een
inor
gani
c le
ad a
nd li
ver o
r oes
opha
geal
can
cer.
Glenn Doolan et al
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014506
Table 3A. Chemical Reviews
Review Country
Method Findings OR(95%CI) Summary
Van Maele-Fabry et al., (2006)
Belguim
Meta Analysis of 18 studies published between 1984 and 2004.
OR = 1.28 [95%CI (1.05-1.58].
A review of cohort studies that examined the occurrence of prostate cancer in pesticide manufacturing workers in order to undertake a qualitative and quantitative evaluation of the risk as well as to assess the level of epidemiological evidence for each class of chemical compounds. After stratification by specific chemical class, consistent increases in the risk of prostate cancer were found in all groups but statistical significance was reported only for accidental or non-accidental exposure to phenoxy herbicides contaminated with dioxins and furans. There was no obvious indication of publication bias. The overall meta-analysis provides additional quantitative evidence consistent with prior reviews focusing on other groups exposed to pesticides (farmers, pesticide applicators). The results again point to occupational exposure to pesticides as a possible risk factor for prostate cancer but the question of causality remains unanswered.
Mink et al., (2008)USA
A Review of eight cohort studies and five case control studies.
No meta-analysis A review of the epidemiologic literature to evaluate the hypothesis that agricultural exposure to pesticides is causally associated with prostate cancer risk. Despite sporadic positive findings, these studies did not show consistently increased risks to support a causal association between agricultural pesticide use and prostate cancer. It is clearly not possible to exonerate any particular pesticide as a putative cause of prostate cancer - to do so would require an inverse empirical association with an upper confidence limit below the null value. Existing evidence does not point to any pesticide as satisfying widely used guidelines for establishing causation: a strong, exposure-dependent and demonstrably unconfounded, unbiased association, documented in several studies.
Prins, (2008)USA
Commentary No meta-analysis This author suggests there is increasing evidence both from epidemiology studies and animal models that specific endocrine-disrupting compounds may influence the development or progression of prostate cancer. In large part, these effects appear to be linked to interference with oestrogen signalling, either through interacting with ERs or by influencing steroid metabolism and altering oestrogen levels within the body. In humans, epidemiologic evidence links specific pesticides, PCBs and inorganic arsenic exposures to elevated prostate cancer risk. There appears to be heightened sensitivity of the prostate during the critical developmental windows including in-utero and neonatal time points as well as during puberty. Thus infants and children may be considered a highly susceptible population for ED exposures and increased risk of prostate cancers with aging.
Ndong et al.,( 2009)France
Review No meta-analysis Diverse studies have consistently demonstrated a higher risk of prostate cancer in agricultural populations than in the general population. The hypothesis that this higher risk is linked to the use of pesticides has been tested in a number of studies, mostly in North America and Europe. However, to date, with a few possible exceptions, it has been impossible to demonstrate a significant association between exposure to pesticides or a chemical family of pesticides and prostate cancer.
Soto & Sonnenschien.,
(2010)USA
Review of over 70 studies as a result of the 1991 Wingspread Conference
No meta-analysis Highlights the carcinogenic properties of Environmental endocrine disrupting chemicals ( EDC’s) . Exposures to EDC’s generate prostate cancer. Looks at the dose effect response at different ages. Examines the usefulness of the adoption of mathematical modelling and computer simulation afforded by system biology approaches. Calls for public health policy on the reduction of the use of EDC’s .
Park et al., (2010)
South Korea
Meta-Analysis Significant decreased deaths from all cancers(SMR = 0.75, 95% CI =
0.62 - 0.90)
Investigate the relationship between low external doses of ionizing radiation exposure and the risk of cancer mortality among nuclear power plant worker from 1990 to January 2009. A total of 11 epidemiologic studies were included. The findings of this meta-analysis were similar with those of the 15 Country Collaborative Study conducted by the International Agency for Research on Cancer. Further studies are needed to clarify the low SMR of cancers, for which there is no useful screening tool, in nuclear power plant workers.
Sathiakumar et al., (2011)
USA
Review of 36 studies on mainly atrazine exposure.
No meta-analysis This is an update of a previous review of epidemiological evidence pertaining to the human carcinogenic potential of triazine herbicides. In the 36 studies evaluated, atrazine was the most common triazine investigated. Non-Hodgkin lymphoma, prostate cancer, and breast cancer were most frequently investigated. Collectively, the available epidemiology studies do not provide consistent, scientifically convincing evidence of a causal relationship between exposure to atrazine or triazine herbicides and prostate cancer in men. Based upon the assessment studies, there is no scientific basis for inferring the existence of a causal relationship between triazine exposure and the occurrence of cancer in humans.
Budnik et al., (2012)
Germany
Systematic review Overall, exposure to me-thyl bromide is associated with an increased risk of
prostate cancer.
Although ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage). Focus is on toxic (especially chronic) or carcinogenic effects from the use of methyl bromide, on bio-monitoring data and reference values. Only 91 referred to toxicity of methyl bromide and 29 used the term “carcinogenic”, “neoplastic” or “mutagenic”. Both the epidemiological evidence and toxicological data suggest a possible link between methyl bromide exposure and serious health problems, including prostate cancer risk from occupational and community exposure. The environmental risks of methyl bromide are not in doubt.
Mullins & Loeb, (2012)USA
Review No Meta-AnalysisOverall, no specific
environmental or oc-cupational exposure has been definitively shown
to cause CaP.
This manuscript reviews the literature on environmental exposures and CaP. While no definitive causative evidence linking CaP and Agent Orange exists, the United States Department of Veteran Affairs considers CaP as related to Agent Orange exposure. While a causative relationship between pesticide exposure and CaP has not been established, the data do suggest that men with significant pesticide exposure may be at increased risk and should be carefully screened. Despite some data demonstrating a direct association between cadmium and CaP risk, the literature does not convincingly implicate cadmium as a cause of CaP. Limiting excessive exposure to cadmium and lead likely has a beneficial impact on overall health and possibly prostate health.
for workers in plastic boat building plants in Ohio and reported excess mortality for prostate cancer associated with styrene exposure. In 2004, Zeegers et al. (2004) reported an increased prostate cancer risk for rubber workers but it was not statistically significant. Manufacturers of rubber tyres use rubber, coal black, sulphur, phenolic resins, chlorine, sulphuric acid and cobalt compounds which would make it difficult to identify a causative agent. A further mortality study (Hauptmann et al., 2004) reported an elevated risk in formaldehyde industry workers for prostate cancer but a dose-response relationship was not reported. Rybicki (2006) reported that petroleum workers with high polycyclic aromatic hydrocarbons (PAH) exposure, and who carry the GSTP1 Val (105) variant allele, were at increased risk of prostate cancer, especially if aged under 60 years or had a family history of the disease. A small Australian case control study (Fritschi et al., 2007) reported non-significant excess risks of prostate cancer associated with occupational exposure to oils other than mineral oil. But a recent USA study (Koutros et al., 2011) reported significant associations between petroleum and prostate cancer. In mining, Girschik et al. (2010) reported Australian miners had a statistically significantly reduced risk of prostate cancer, which may be explained by the healthy worker effect.
More recently, exposure to PAHs was implicated in prostate carcinogenesis by a prospective study of 15 million Scandinavians that reported elevated SIRs (Pukkala, 2009) for chimney sweeps and hairdressers. Chimney sweeps are exposed to carcinogens such as PAHs from chimney soot and the work environment of hairdressers has also varied over time with respect to exposure to chemical agents. In the vehicle manufacturing industry, mortality rates are reported to be higher than expected for workers in casting operations (Delzell et al., 2003) where exposure to oil-based fluid use is part of the production process. Exposure of auto industry workers to oil-based fluids was reported to be modestly associated with prostate cancer with a latency period of at least 25 years (Agalliu et al., 2005a; 2005b). Prince et al. (2006) reported that electrical capacitor manufacturing workers exposed to polychlorinated biphenyls (PCBs) had increased prostate cancer mortality associated with cumulative PCB exposure. We identified three recent reviews by Van Maele-Fabry et al. (2006) Mink et al. (2008) and Ndong et al. (2009) of exposure to pesticides, herbicides and insecticides. The first review by Van Maele-Fabry et al. (2006) included 18 cohort studies of prostate cancer risk in pesticide manufacturing workers. A qualitative
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014 507
DOI:http://dx.doi.org/10.7314/APJCP.2014.15.2.501An Update on Occupation and Prostate Cancer
and quantitative evaluation of the risk was assessed together with the level of epidemiological evidence for each class of chemical compounds used between 1984 and 2004. Meta-analyses were performed for each chemical class separately, resulting in a meta-rate ratio estimate for all studies of 1.28 (95%CI= 1.05-1.58). Consistent increases in the risk of prostate cancer were observed for all chemical classes but statistically significant increases in risk were observed only for exposure to phenoxy herbicides contaminated with dioxins and furans, and a recent study (Burns et al., 2011) reported fewer cancer cases were observed than expected. Mink et al. (2008) analyzed eight cohort studies and five case-control studies that quantified and/or evaluated agricultural exposure to particular pesticide classes or chemicals. Although there were some positive findings, these studies did not show sufficiently consistent increased risks to support a causal association between agricultural pesticide use and prostate cancer. Mink et al. (2008) argued strenuously those studies of prostate cancer that use an ‘external’ comparison group must be interpreted in the context of confounding by differences in prostate-specific antigen (PSA) screening intensity. They further identified that most studies failed to adjust for potential confounders other than age and time period and concluded that it was clearly not possible to exonerate any particular pesticide as a putative cause of prostate cancer. Studies of agricultural workers have consistently demonstrated a higher risk of prostate cancer compared with the general population (Ndong et al., 2009). The hypothesis that risks to agricultural workers might be linked to the use of pesticides has been investigated in a number of studies, mostly in North America and Europe. With only a few limited exceptions such as Koutros et al. (2010a; 2011) it has not been demonstrated that a significant association between exposures to pesticides, or a chemical family of pesticides, and prostate cancer exists. The pesticides studies are summarised in Table 3 which includes limited evidence of elevated risk of prostate cancer in relation to exposure to organochlorines (Kumar et al., 2010; Sawada et al., 2010). Organochlorines, which have the capacity to move up the food chain and bioaccumulate in the fat of large animals and humans, affect the nervous system in particular and also have an association with prostate cancer. Other authors (Prins, 2008) have indicated that infants and children may be considered susceptible to Endocrine Disrupting Chemical (EDC’s) exposure and increased risk of prostate cancer with aging. Soto and Sonnenschein (2010) have reported that exposure to EDC’s generates prostate cancer as well as other cardiovascular and thyroid endocrinology. Of recent interest is the finding of a novel study (St-Hilaire et al., 2010) of weather patterns in the USA that finds there is a higher rate of prostate cancer in the North, than in the South of the USA. The study relates this finding to organic pollutants and pesticides that are endocrine disrupting chemicals. Insecticides (2003) also showed an increase in risk among farmers exposed to organochlorine insecticides and acaricides (OR=2.5, 95%CI=1.4-4.2) and DDT (OR=2.1, 95%CI=1.2-3.8) and dicofol, (OR=2.8, 95%CI= 1.5-5.0).
Recently a study (Cockburn et al., 2011) reported an association between prostate cancer and methyl bromide OR=1.62 (95%CI=1.02-2.59) and a review (Budnik et al., 2012) on methyl bromide, which was used as a soil fumigant against pests, reported it to be significantly associated with prostate cancer with an OR of 1.21 (95%CI 0.98-1.49) but the p value was >0.05. A number of other studies have examined the more recently available and commonly used organophosphate insecticides which include the early biological warfare agents such as nerve gas or the more modern Sarin gas. Organophosphate insecticides used primarily in farming affect acetylcholine control in nerve stimulation, such as Phorate (sometimes in combination with family history, (Mahajan et al., 2006b) Fonfos (Mahajan et al., 2006a; Koutros et al., 2010b; Barry et al., 2011; 2012), Coumaphos (Christensen et al., 2010) and fumigants, such as triazine herbicides (Mills and Yang, 2003), all were reported to contribute to a small increased risk of prostate cancer. Atrazine was also investigated by Hessel et al. (2004) but no association was reported with prostate cancer. This was supported recently by Sathiakumar et al. (2011), who indicated that there was no scientific basis for inferring the existence of a causal relationship between triazine exposure and the occurrence of cancer in humans. Pesticides in general have been investigated by a number of researchers (Boers et al., 2005; Fritschi et al., 2007; Strom et al., 2008; Lynch et al., 2009; Subahir et al., 2009; Xu et al., 2010; Band et al., 2011) with some studies reporting weak associations with prostate cancer and another (Mullins et al., 2012) concluding overall there are no specific environmental or occupational exposure identified that causes prostate cancer. A recent study from Martinique (Landau-Ossondo et al., 2009) considered that pesticides and especially organochlorine pesticides could be causally associated with prostate cancer due to their carcinogenic properties. This was also supported by Xu et al. (2010) and suggested a reduction in world-wide use of OC’s. However, two other studies, Boers et al. (2005) and Fritschi et al. (2007) failed to find a significant association with pesticides. Furthermore, no association is reported with cyanazine exposure (Lynch et al., 2006) or metachlor exposure (also found in surface and ground water). Metachlor was reported to have a significantly decreased relative risk with prostate cancer (2006). Aronson et al. (2010) and Sawada et al. (2010) also suggest that long term low-level exposure to organochlorine pesticides and PCBs in the general population does not contribute to increased prostate cancer. A recent Australian study by Macfarlane et al. (2009) examined the occupational classification of workers who were exposed to pesticides and concluded that only about 30% of farm workers actually came in contact with pesticides, herbicides or insecticides and, therefore, the level of pesticide exposure for this group of workers may be over estimated.
Ergonomic factors Ergonomic factors include inconvenient and difficult work postures, manual handling of burdens, occupational
Glenn Doolan et al
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014508
Tabl
e 3B
. Che
mic
al S
tudi
es
Stud
yC
ount
ryC
ases
(N
)C
ontr
ols
(N)
Find
ings
OR
(95%
CI)
Sum
mar
y
Del
zell,
et a
l., (2
003)
UK
40,1
31 o
bs.
deat
hs43
,859
expe
cted
dea
ths
Pros
tate
Can
cer (
SMR
= 1
28, C
I = 1
02-1
58)
198,
245
mot
or v
ehic
le in
dust
ry w
orke
rs d
urin
g th
e pe
riod
of 1
973
to 1
995.
Mor
talit
y ra
tes w
ere
high
er th
an e
xpec
ted
for p
rost
ate
canc
er in
cas
ting
oper
atio
ns.
Mill
s et a
l., (2
003)
USA
222
1110
CaP
in M
ushr
oom
Far
mer
s OR
=1.9
1, (9
5% C
I = 0
.87
-4.1
8)Fa
rm w
orke
rs w
ith re
lativ
ely
high
leve
ls o
f exp
osur
e to
org
anoc
hlor
ine,
org
anop
hosp
hate
pes
ticid
es, f
umig
ants
, or t
riazi
ne h
erbi
cide
s exp
erie
nced
ele
vate
d ris
k of
pro
stat
e ca
ncer
com
pare
d to
wor
kers
w
ith lo
wer
leve
ls o
f exp
osur
e.
Setti
mi e
t al.,
(200
3)Ita
ly12
465
9PC
a &
Tob
. (O
R=2
.1, 9
5%C
I=1.
1-4.
1) P
Ca
& C
hem
. (O
R=2
.2, 9
5%C
I=0.
7-7.
2)O
CI &
aca
ricid
e (O
R=2
.5, 9
5%C
I=1.
4-4.
2) D
icof
ol (O
R=2
.8, 9
5%C
I=1.
5-5.
0)Pr
osta
te c
ance
r is r
elat
ed p
ositi
vely
to fo
od a
nd to
bacc
o an
d ch
emic
al p
rodu
cts i
ndus
tries
. The
ass
ocia
tion
betw
een
diffe
rent
type
s of p
estic
ides
and
pro
stat
e ca
ncer
show
ed in
crea
sed
risks
am
ong
farm
-er
s exp
osed
to o
rgan
ochl
orin
e in
sect
icid
es a
nd a
caric
ides
, mor
e sp
ecifi
cally
to th
e of
ten
cont
empo
rary
use
d co
mpo
unds
DD
T, a
nd d
icof
ol, w
hose
effe
cts c
ould
not
be
wel
l sep
arat
ed.
Rud
er e
t al.,
(200
4)U
SA86
0 de
aths
5,20
4w
orke
rsD
eath
s SM
R 1
.09,
95%
CI 1
.02-
1.17
) PC
a SM
R 1
.71,
95%
CI 1
.09-
2.54
)A
coh
ort s
tudy
, in
whi
ch 5
,204
wor
kers
exp
osed
to st
yren
e be
twee
n 19
59 a
nd 1
978
at tw
o re
info
rced
pla
stic
boa
tbui
ldin
g pl
ants
. Una
ntic
ipat
ed e
xces
s urin
ary
tract
can
cer a
nd re
spira
tory
dis
ease
m
orta
lity,
pos
sibl
y as
soci
ated
with
styr
ene
expo
sure
, wer
e di
fficu
lt to
inte
rpre
t and
cou
ld b
e ch
ance
find
ings
. Exc
ess m
orta
lity
for C
aP.
Zeeg
ers e
t al.,
(200
4)H
olla
nd83
015
25R
R =
4.1
8 (9
9% C
I = 0
.22
- 80.
45) R
ubbe
rR
R =
3.9
1 (9
9% C
I = 1
.14-
3.42
) Pol
icem
enR
R =
4.0
0 (9
9% C
I = 1
.19-
13.3
7) p
olic
e la
st p
rofe
ssio
n
Pros
pect
ive
coho
rt st
udy
(N=5
8,27
9) w
ho re
porte
d to
hav
e ev
er w
orke
d in
the
rubb
er in
dust
ry, i
t was
repo
rted
that
a su
bsta
ntia
lly in
crea
sed
pros
tate
can
cer r
isk,
but
not
stat
istic
ally
sign
ifica
nt. F
or
polic
emen
, the
y re
porte
d a
subs
tant
ial a
nd m
argi
nally
stat
istic
ally
sign
ifica
nt in
crea
sed
pros
tate
can
cer r
isk,
esp
ecia
lly fo
r tho
se w
ho re
porte
d w
orki
ng a
s a p
olic
eman
for m
ost o
f the
ir oc
cupa
tiona
l life
or
as t
he la
st p
rofe
ssio
n he
ld a
t bas
elin
e.
Hau
ptm
ann
et a
l.,
(200
4)U
SA
1,92
1 de
aths
25,6
19
wor
kers
Pop.
SM
R =
0.9
1 S
tudy
SM
R =
0.7
8 C
ohor
t stu
dy o
f mor
talit
y fr
om so
lid c
ance
rs a
mon
g w
orke
rs in
form
alde
hyde
indu
strie
s. A
lthou
gh re
lativ
e ris
ks fo
r pro
stat
e ca
ncer
(145
dea
ths)
wer
e el
evat
ed fo
r som
e m
easu
res o
f for
mal
dehy
de
expo
sure
, the
tren
d w
as in
cons
iste
nt. S
ome
evid
ence
was
repo
rted
of a
n ex
posu
re-r
espo
nse
rela
tion
with
mor
talit
y fr
om o
ther
can
cers
but
not
for c
ance
r of t
he p
rost
ate.
Hes
sel,
et a
l., (2
004)
USA
1213
0O
R =
8.5
4; (9
5% C
I 1.6
9-82
.20)
> o
r = 1
A st
udy
of p
rost
ate
canc
er a
nd a
trazi
ne e
xpos
ure.
Cas
es h
ad m
ore
PSA
test
s tha
n co
ntro
l sub
ject
s. Th
ere
was
no
asso
ciat
ion
betw
een
atra
zine
exp
osur
e an
d pr
osta
te c
ance
r whe
n th
ose
with
> o
r =1
test
w
ere
com
pare
d.
Aga
lliu
et a
l., (2
005)
USA
872
4360
RR
= 2
.4 p
er 1
0 m
g/m
(3 )-ye
ars
Ris
k of
pro
stat
e ca
ncer
line
arly
incr
ease
d w
ith e
xpos
ure
to st
raig
ht A
utow
orke
rs e
xpos
ed to
Met
al W
orki
ng F
luid
(MW
F) a
nd a
t a y
oung
age
als
o ha
d an
incr
ease
d ris
k as
soci
ated
with
MW
F ex
posu
re
incu
rred
late
r in
life.
For
solu
ble
MW
F th
ere
was
a sl
ight
ly in
crea
sed
risk
in th
e th
ird w
indo
w.
Aga
lliu
et a
l., (2
005)
USA
872
4360
RR
= 1.
12 p
er 1
0mg/
m-y
ears
of e
xpos
ure
(95%
CI 1
.04-
1.20
)Ex
posu
re to
oil-
base
d flu
ids,
solu
ble
and
stra
ight
, is m
odes
tly a
ssoc
iate
d w
ith p
rost
ate
canc
er ri
sk a
mon
g au
tow
orke
rs, w
ith a
late
ncy
perio
d of
at l
east
25
year
s.
Boe
rs, (
2005
)H
olla
nd13
8623
35m
etal
dus
t (R
R 1
.01;
95%
CI 0
.72
to 1
.40)
met
al fu
mes
(RR
1.1
1; 9
5% C
I 0.8
0 to
1.5
4)W
hen
com
parin
g th
e hi
ghes
t ter
tile
of e
xpos
ure
with
no
expo
sure
ther
e w
as a
neg
ativ
e as
soci
atio
n fo
r pes
ticid
es. N
o as
soci
atio
n w
as re
porte
d fo
r occ
upat
iona
l exp
osur
e to
PA
Hs,
dies
el e
xhau
st, m
etal
du
st, m
etal
fum
es a
nd m
iner
al o
il.
Prin
ce e
t al.,
(200
6)U
SA14
614
458
PCa
- 34
deat
hs; S
MR
1.0
4; (9
5% C
I, 0.
72-1
.45)
, in
crea
sed
with
Cum
. Exp
osur
e. (t
rend
p-v
alue
=0.0
001)
N=1
4,45
8 el
ectri
cal c
apac
itor m
anuf
actu
ring
wor
kers
exp
osed
PC
Bs.
Cum
ulat
ive
PCB
exp
osur
e w
as e
stim
ated
usi
ng a
new
job
expo
sure
mat
rix. T
his w
as th
e fir
st P
CB
coh
ort s
how
ing
a st
rong
ex
posu
re-r
espo
nse
rela
tions
hip
for p
rost
ate
canc
er m
orta
lity.
Lync
h et
al.,
(200
6)U
SA20
,824
57,3
11PC
a R
R=1
.23
(95%
CI,
0.87
-1.7
0)C
ance
r inc
iden
ce a
mon
g pe
stic
ide
appl
icat
ors e
xpos
ed to
cya
nazi
ne in
the A
gric
ultu
ral H
ealth
Stu
dy (A
HS)
. No
clea
r or c
onsi
sten
t ass
ocia
tions
bet
wee
n cy
anaz
ine
expo
sure
and
any
can
cer a
naly
zed.
Rybi
cki e
t al.
(200
6)U
SA63
724
4<6
0 O
R=
4.52
(95%
CI=
1.96
-10.
41)/+
F.H
. OR
= 3.
02 (9
5% C
I=1.
15-7
.92)
.Pr
osta
te c
ance
r ris
k fr
om o
ccup
atio
nal e
xpos
ure
to P
AH
s int
erac
ting
with
the
GST
P1 Il
e105
Val p
olym
orph
ism
The
se re
sults
sugg
est m
en w
ho c
arry
the
GST
P1 V
al(1
05) v
aria
nt a
nd a
re e
xpos
ed a
t hi
gh le
vels
to o
ccup
atio
nal P
AH
hav
e in
crea
sed
risk
for p
rost
ate
canc
er.
Rus
ieck
i, et
al.,
(200
6)U
SA50
,193
PCa
LTD
RR
=0.5
9 (9
5% C
I=0.
39-0
.89)
/PC
a IW
LD R
R =
0.6
6 (9
5%C
I=0.
45-0
.97)
No
clea
r ris
k fo
r any
can
cer s
ubty
pe w
as re
porte
d fo
r exp
osur
e to
met
olac
hlor
. A si
gnifi
cant
ly d
ecre
ased
RR
was
repo
rted
for p
rost
ate
canc
er in
the
high
est c
ateg
ory
of li
fetim
e da
ys’ e
xpos
ure
and
in
the
seco
nd h
ighe
st c
ateg
ory
of in
tens
ity-w
eigh
ted
lifet
ime
days
exp
osur
e; h
owev
er, t
he te
st fo
r tre
nd w
as n
ot si
gnifi
cant
for e
ither
exp
osur
e m
etric
.
Mah
ajan
et a
l., (2
006)
USA
45,3
72PC
a R
R =
1.53
(95%
CI =
0.9
9 - 2
.37)
Alth
ough
pro
stat
e ca
ncer
risk
was
not
sign
ifica
ntly
rela
ted
to p
hora
te (a
pop
ular
pes
ticid
e) u
se o
vera
ll or
am
ong
thos
e w
ithou
t a fa
mily
his
tory
, the
risk
tend
ed to
incr
ease
am
ong
appl
icat
ors w
ith a
fa
mily
his
tory
of p
rost
ate
canc
er. T
he o
bser
ved
stat
istic
al in
tera
ctio
n su
gges
ts a
gen
e-en
viro
nmen
t int
erac
tion
betw
een
fam
ily h
isto
ry a
nd p
hora
te e
xpos
ure
in th
e in
cide
nce
of p
rost
ate
canc
er, b
ut o
ther
ex
plan
atio
ns a
re a
lso
poss
ible
.
Mah
ajan
et a
l, (2
006)
USA
45,3
72a
sign
ifica
nt d
ose-
resp
onse
tren
d fo
r life
time
expo
sure
-day
s (P
trend
=0.0
2). h
ighe
st v
s un
expo
sed:
RR
=1.7
7 (9
5%C
I=1.
03-3
.05)
/Inte
ract
ion
RR
=1.2
8 (9
5%C
I= 1
.07-
1.54
)A
lthou
gh p
rost
ate
canc
er ri
sk w
as u
nrel
ated
to fo
nfos
use
ove
rall,
am
ong
appl
icat
ors w
ith a
fam
ily h
isto
ry o
f pro
stat
e ca
ncer
, we
obse
rved
a si
gnifi
cant
dos
e-re
spon
se tr
end
for l
ifetim
e ex
posu
re-
days
. Int
ensi
ty-w
eigh
ted
resu
lts w
ere
sim
ilar.
Furth
er st
udy
is w
arra
nted
to c
onfir
m fi
ndin
gs w
ith re
spec
t to
leuk
emia
and
det
erm
ine
whe
ther
gen
etic
susc
eptib
ility
mod
ifies
pro
stat
e ca
ncer
risk
from
pe
stic
ide
expo
sure
.
Frits
chi e
t al.,
(200
7)A
ustra
lia60
6 PC
a 40
0 B
PH47
1B
PH O
R=1
.39
(95%
CI=
1.1
to 1
.84)
PC
a O
R=1
.25
(95%
CI=
0.96
to 1
.61)
Oils
OR
=1.5
4 (5
%C
I=0.
95 to
2.5
1) P
AH
s OR
=1.2
0 (9
5%C
I=0.
91 to
1.5
8)O
PP’s
OR
=0. 6
9 (9
5%C
I=0.
43 to
1.1
2).
Expo
sure
to to
xic
met
als a
t a n
on-s
ubst
antia
l lev
el in
crea
sed
the
risk
of B
PH a
nd le
d to
a n
on-s
igni
fican
t exc
ess r
isk
of p
rost
ate
canc
er. N
on-s
igni
fican
t exc
ess r
isks
wer
e ob
serv
ed fo
r pro
stat
e ca
ncer
af
ter e
xpos
ure
to o
ils o
ther
than
min
eral
oil
and
for B
PH a
fter e
xpos
ure
to P
AH
s. A
non
-sta
tistic
ally
sign
ifica
nt p
rote
ctiv
e ef
fect
for p
rost
ate
canc
er w
as se
en a
fter e
xpos
ure
to o
rgan
opho
spha
te p
esti-
cide
s. N
o ot
her a
ssoc
iatio
ns w
ere
repo
rted
for e
ither
pro
stat
e ca
ncer
or B
PH a
nd n
o do
se-r
espo
nse
rela
tions
hips
wer
e se
en fo
r the
exp
osur
es in
vest
igat
ed.
Stro
m e
t al.,
(200
8)U
SA17
617
4ob
esity
at t
ime
of d
iagn
osis
: OR
= 2
.50
(95%
CI =
1.2
0 - 5
.20
agric
hem
ical
exp
osur
e: O
R =
4.6
5 (9
5% C
I = 1
.97-
10.9
7In
crea
sed
risk
of b
eing
dia
gnos
ed w
ith a
dvan
ced
PCa
was
ass
ocia
ted
with
obe
sity
at t
ime
of d
iagn
osis
and
hig
h le
vels
of a
gric
hem
ical
exp
osur
e. T
his c
ase-
cont
rol s
tudy
, the
firs
t con
duct
ed in
a
hom
ogen
eous
His
pani
c po
pula
tion,
iden
tified
mod
ifiab
le P
Ca
risk
fact
ors,
such
as a
gric
hem
ical
exp
osur
e, w
hich
may
be
usef
ul in
dev
elop
ing
inte
rven
tions
for t
his u
nder
stud
ied
popu
latio
n. A
n in
vers
e re
latio
nshi
p be
twee
n lo
w a
nd h
igh
activ
ity le
vels
.
Mac
Farla
ne e
t al.,
(2
009)
Aus
tralia
1172
Like
ly P
estic
ide
Expo
sure
=68%
/Far
m Jo
bs &
Unl
ikel
y pe
stic
ide
expo
sure
= 7
8.3%
Mos
t (68
.8%
) job
s with
like
ly p
estic
ide
expo
sure
wer
e fa
rm jo
bs, b
ut 7
8.3%
of f
arm
jobs
wer
e as
sess
ed a
s hav
ing
no li
kelih
ood
of p
estic
ide
expo
sure
. Cla
ssifi
catio
n of
all
farm
jobs
as p
estic
ide
expo
sed
is li
kely
to su
bsta
ntia
lly o
ver-e
stim
ate
the
num
ber o
f ind
ivid
uals
exp
osed
.
Lync
h et
al.,
(200
9)U
SA52
9714
,358
PC a
RR
(LD
) = 2
.09
(95%
CI =
1.27
- 3.
44)
PCa
+FH
RR
(LD
) =2.
00 (9
5% C
I=1.
07-3
.74)
Pros
tate
can
cer r
isk
was
sign
ifica
ntly
ele
vate
d am
ong
appl
icat
ors i
n th
e hi
ghes
t LD
cat
egor
y in
bot
h re
fere
nt g
roup
s. A
sign
ifica
ntly
ele
vate
d jo
int e
ffect
of p
rost
ate
canc
er fa
mily
his
tory
and
hig
h bu
tyla
te u
sage
acr
oss b
oth
expo
sure
met
rics a
nd b
oth
refe
rent
gro
ups,
and
a no
n-si
gnifi
cant
, ele
vate
d in
tera
ctio
n be
twee
n bu
tyla
te u
se a
nd p
rost
ate
canc
er fa
mily
his
tory
(F.H
.).
Pukk
ala
et a
l., (2
009)
Finl
and
2.8M
15 M
Dom
estic
ass
t. SI
R=0
.79
(95%
CI=
0.66
-.95)
Wai
ters
SI=
1.48
(95%
CI=
1.43
-1.5
4)C
him
ney
S/s S
IR=1
.03
(95%
CI=
1.03
-1.1
7)C
him
ney
swee
ps a
re e
xpos
ed to
car
cino
gens
such
as p
olyc
yclic
aro
mat
ic h
ydro
carb
ons f
rom
the
chim
ney
soot
, and
hai
rdre
sser
s’ w
ork
envi
ronm
ent i
s als
o ric
h in
che
mic
al a
gent
s.
Suba
hir e
t al.,
(200
9)M
alay
sia
112
112
Pest
icid
e ex
posu
re O
R =
5.5
7 (9
5%C
I=1.
75 -
17.7
8)So
me
lifes
tyle
and
occ
upat
ion
fact
ors a
re st
rong
pre
dict
ors o
f the
occ
urre
nce
of p
rost
ate
canc
er a
mon
g pa
tient
s in
Mal
aysi
a. W
hils
t fre
quen
t ing
estio
n of
tom
atoe
s and
veg
etab
les a
nd se
xual
inte
r-co
urse
wer
e pr
otec
tive.
Land
au-O
sson
do
et a
l., (2
009)
Mar
tiniq
ue
Epid
emio
logi
cal c
ompa
rison
of t
wo
popu
latio
ns d
emog
raph
ic d
ata
IR in
Fra
nce
152.
7/10
0,00
0IR
in M
artin
ique
75.
3/10
0,00
0U
sing
a li
near
regr
essi
on a
naly
sis,
it w
as re
porte
d th
at th
e gr
owth
cur
ves o
f inc
iden
ce ra
tes f
or M
artin
ique
and
met
ropo
litan
Fra
nce
have
bee
n si
gnifi
cant
ly d
iver
ging
sinc
e 19
83. A
lthou
gh a
Car
ibbe
an
gene
tic su
scep
tibili
ty fa
ctor
may
be
invo
lved
in p
rost
ate
carc
inog
enes
is: t
his f
acto
r, be
caus
e it
coul
d no
t hav
e ch
ange
d du
ring
the
obse
rvat
ion
perio
d, c
anno
t per
se a
ccou
nt fo
r the
gro
win
g in
cide
nce
of th
is c
ance
r in
the
isla
nd. P
estic
ides
and
esp
ecia
lly o
rgan
ochl
orin
e pe
stic
ides
may
be
caus
ally
impl
icat
ed in
the
grow
ing
inci
denc
e of
pro
stat
e ca
ncer
in M
artin
ique
due
to th
eir c
arci
noge
nic
prop
er-
ties.
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014 509
DOI:http://dx.doi.org/10.7314/APJCP.2014.15.2.501An Update on Occupation and Prostate Cancer
Tabl
e 3B
(con
tinue
). C
hem
ical
Stu
dies
Stud
yC
ount
ryC
ases
(N
)C
ontro
ls(N
)Fi
ndin
gs O
R(9
5%C
I)Su
mm
ary
Xu
et a
l., (2
010)
USA
654,
109
HC
H (p
for t
rend
=0.0
2)/T
rans
-non
achl
or (p
for t
rend
= 0
.002
)D
ield
rin (p
for t
rend
= 0
.04)
Ass
ocia
tions
bet
wee
n se
rum
con
cent
ratio
ns o
f OC
pes
ticid
es a
nd p
rost
ate
canc
ers i
n U
S ad
ults
. Res
ults
wer
e si
gnifi
cant
ly a
ssoc
iate
d w
ith th
e ris
k of
pre
vale
nt p
rost
ate
canc
er in
this
coh
ort
stud
y. T
hese
resu
lts su
gges
t tha
t OC
pes
ticid
e ex
posu
res m
ay h
ave
a si
gnifi
cant
effe
ct o
n ca
ncer
risk
. Effo
rts to
redu
ce w
orld
wid
e O
C u
se a
re w
arra
nted
.
Kum
ar e
t al.,
(201
0)In
dia
7061
beta
-HC
H p
= 0
.04/
gam
ma-
HC
H p
= 0
.008
/p,p
’-D
DE
p=0.
01 a
dvan
ced
stag
es o
f PC
aga
mm
a-H
CH
(<or
=T(2
) vs.
>or=
T(3)
), (p
=0.0
4)H
ighe
r lev
els o
f org
anoc
hlor
ines
, esp
ecia
lly b
eta-
HC
H, g
amm
a-H
CH
and
p,p
’-D
DE
mig
ht b
e as
soci
ated
with
pro
stat
e ca
ncer
risk
.
Girs
chik
et a
l., (2
010)
Aus
tralia
604
466
adju
sted
OR
0.3
5, (9
5% C
I = 0
.16
to 0
.75)
In th
is p
opul
atio
n ba
sed
case
con
trol s
tudy
, min
ers h
ad a
stat
istic
ally
sign
ifica
ntly
redu
ced
risk
of p
rost
ate
canc
er. T
he sy
stem
atic
lite
ratu
re se
arch
of s
tudi
es e
xam
inin
g m
inin
g an
d pr
osta
te
canc
er re
porte
d a
reas
onab
ly c
onsi
sten
t tre
nd o
f a d
ecre
ased
risk
of p
rost
ate
canc
er a
mon
g m
iner
s.
Aro
nson
, et a
l., (2
010)
Can
ada
7932
9PC
B c
onge
ners
+ to
tal P
CB
s OR
< 1
.0M
ost P
estic
ides
clo
se to
nul
l.Th
is c
ase-
cont
rol s
tudy
sugg
ests
that
long
-term
low
-leve
l exp
osur
e to
org
anoc
hlor
ine
pest
icid
es a
nd P
CB
s in
the
gene
ral p
opul
atio
n do
es n
ot c
ontri
bute
to in
crea
sed
pros
tate
can
cer
risk.
Chr
iste
nsen
et a
l., (2
010)
USA
1,19
644
,133
PCa
+ (F
.H.)
RR
= 2
.07
(95%
CI =
1.1
9-3.
62)
p-in
tera
ctio
n =
0.00
5C
umul
ativ
e ex
posu
re to
cou
map
hos (
com
mon
pes
ticid
e) w
as n
ot a
ssoc
iate
d w
ith c
ance
r ris
k ov
eral
l or w
ith p
rost
ate
canc
er. I
n m
en w
ith F
.H. o
f pro
stat
e ca
ncer
, a p
ositi
ve a
ssoc
iatio
n be
twee
n ev
er u
se o
f cou
map
hos a
nd p
rost
ate
canc
er in
bot
h ea
rly a
nd la
ter p
erio
ds o
f fol
low
-up
was
obs
erve
d. In
men
with
a fa
mily
his
tory
of d
isea
se, t
here
was
evi
denc
e of
an
asso
ciat
ion
betw
een
coum
apho
s and
pro
stat
e ca
ncer
,
Saw
ada
et a
l., (2
010)
Japa
n20
140
2N
o st
atis
tical
ly si
gnifi
cant
ass
ocia
tion
with
tota
l pro
stat
e ca
ncer
was
seen
for a
ny p
lasm
a or
gano
chlo
rine,
A n
este
d ca
se-c
ontro
l stu
dy u
sing
dat
a fr
om th
e Ja
pan
Publ
ic H
ealth
Cen
ter-b
ased
Pro
spec
tive
(JPH
C) S
tudy
. A to
tal o
f 14,
203
men
40-
69 y
ears
old
who
retu
rned
the
base
line
ques
tionn
aire
an
d w
ho p
rovi
ded
bloo
d sa
mpl
es w
ere
follo
wed
from
199
0 to
200
5 an
d th
e re
sear
cher
s ide
ntifi
ed 2
01 p
artic
ipan
ts w
ho w
ere
new
ly d
iagn
osed
with
pro
stat
e ca
ncer
. Tw
o m
atch
ed c
ontro
ls
for e
ach
case
wer
e se
lect
ed fr
om th
e co
hort.
The
aut
hors
obs
erve
d an
insi
gnifi
cant
inve
rse
asso
ciat
ion
for p
lasm
a H
CB
and
[bet
a]-H
CH
. Tot
al P
CB
in p
lasm
a w
as a
lso
inve
rsel
y as
soci
ated
w
ith a
dvan
ced
pros
tate
can
cer b
ut w
ithou
t sta
tistic
al si
gnifi
canc
e.
Kou
tros,
et a
l., (2
010)
USA
776
1,44
4Fo
nofo
s sub
ject
s with
thre
e or
four
risk
alle
les a
t rs7
8373
28 a
nd rs
4242
382
had
appr
oxim
atel
y th
ree
times
th
e ris
k of
pro
stat
e ca
ncer
(OR
, 3.1
4; 9
5% C
I, 1.
41–7
.00)
com
pare
d w
ith su
bjec
ts w
ho h
ad z
ero
risk
alle
les
and
neve
r use
d fo
nofo
s.
Gen
ome-
wid
e as
soci
atio
n st
udie
s hav
e id
entifi
ed 8
q24
regi
on v
aria
nts a
s ris
k fa
ctor
s for
pro
stat
e ca
ncer
. In
the A
gric
ultu
ral H
ealth
Stu
dy, a
pro
spec
tive
stud
y of
lice
nsed
pes
ticid
e ap
plic
ator
s, it
was
obs
erve
d th
at th
ere
was
an
incr
ease
d Pr
osta
te c
ance
r ris
k w
ith sp
ecifi
c pe
stic
ide
use
amon
g th
ose
with
a fa
mily
his
tory
of p
rost
ate
canc
er. A
lso
obse
rved
a si
gnifi
cant
inte
ract
ion
amon
g va
riant
s on
chro
mos
ome
8q24
, pes
ticid
e us
e, a
nd ri
sk o
f pro
stat
e ca
ncer
. Ins
ectic
ides
, par
ticul
arly
or
gano
phos
phat
es, w
ere
the
stro
nges
t mod
ifier
s of r
isk,
alth
ough
the
biol
ogic
al m
echa
nism
is u
ncle
ar. T
his i
s the
firs
t rep
ort o
f effe
ct m
odifi
catio
n be
twee
n 8q
24 a
nd a
n en
viro
nmen
tal
expo
sure
on
pros
tate
can
cer r
isk.
Kou
tros,
et a
l., (2
010)
USA
776
1,44
4A
sign
ifica
nt e
xces
s of p
rost
ate
canc
er w
as se
en fo
r priv
ate
appl
icat
ors (
SIR
=1.1
9, 9
5% C
I 1.1
4, 1
.25
and
com
mer
cial
app
licat
ors S
IR=1
.28,
95%
CI=
1.00
, 1.6
1).
A re
-eva
luat
ion
of c
ance
r inc
iden
ce a
mon
g A
gric
ultu
ral H
ealth
Stu
dy p
artic
ipan
ts. S
tand
ardi
zed
inci
denc
e ra
tios (
SIR
s) a
nd re
lativ
e st
anda
rdiz
ed ra
tios w
ere
calc
ulat
ed. A
lthou
gh lo
wer
ra
tes o
f sm
okin
g an
d in
crea
sed
phys
ical
act
ivity
pro
babl
y co
ntrib
ute
to th
e lo
wer
ove
rall
canc
er in
cide
nce,
agr
icul
tura
l exp
osur
es in
clud
ing
pest
icid
es, v
iruse
s, ba
cter
ia, s
unlig
ht, a
nd o
ther
ch
emic
als m
ay in
crea
se ri
sks f
or sp
ecifi
c ca
ncer
site
s.
Kum
ar e
t al.,
(201
0)In
dia
7061
Hig
her l
evel
s of c
-HC
H w
ere
obse
rved
in a
dvan
ced
stag
es o
f pro
stat
e ca
ncer
cas
es (6
T2 v
s.PT3
), (p
-val
ue =
0.
04).
Die
ldrin
was
repo
rted
sign
ifica
ntly
hig
her i
n ca
ses w
ith in
itial
stag
es (p
-val
ue =
0.0
3).
Org
anoc
hlor
ine
pest
icid
es (O
CPs
) and
pol
ymor
phis
ms o
f xen
obio
tic m
etab
oliz
ing
enzy
mes
are
repo
rted
to b
e as
soci
ated
with
the
poss
ible
risk
of p
rost
ate
canc
er. O
CPs
are
end
ocrin
e di
s-ru
ptor
s (ED
s) w
hich
may
act
by
disr
uptin
g th
e ph
ysio
logi
c fu
nctio
n of
end
ogen
ous h
orm
ones
and
ther
efor
e po
ssib
ly in
crea
se p
rost
ate
canc
er ri
sk. C
YP1
A1
met
abol
izes
seve
ral c
arci
noge
ns
and
estro
gens
, etc
. and
hen
ce p
olym
orph
ism
of t
his g
ene
has b
een
repo
rted
to b
e as
soci
ated
with
pro
stat
e ca
ncer
risk
. The
rese
arch
ers d
id n
ot o
bser
ve a
ny c
orre
latio
n be
twee
n pr
osta
te
canc
er a
nd C
YP1
A1
poly
mor
phis
ms.
Hen
ce, h
ighe
r lev
el o
f OC
Ps, e
spec
ially
b-H
CH
, c-H
CH
and
p,p
0-D
DE
mig
ht b
e as
soci
ated
with
pro
stat
e ca
ncer
risk
.
St-H
ilaire
et a
l.(20
10)
USA
Met
eoro
logi
cal
anal
ysis
Ther
e ex
ists
a n
orth
-sou
th p
atte
rn to
the
dist
ribut
ion
of p
rost
ate
canc
er in
the
U.S
., w
ith th
e no
rth h
avin
g hi
gher
rate
s tha
n th
e so
uth.
The
cur
rent
hyp
othe
sis f
or th
e sp
atia
l pat
tern
of t
his
dise
ase
is lo
w v
itam
in D
leve
ls in
indi
vidu
als l
ivin
g at
nor
ther
ly la
titud
es; h
owev
er, t
his e
xpla
natio
n on
ly p
artia
lly e
xpla
ins t
he sp
atia
l dis
tribu
tion
in th
e in
cide
nce
of th
is c
ance
r. Th
e tre
nds
repo
rted
in th
is U
SA st
udy
sugg
est p
rost
ate
canc
er m
ay b
e pa
rtial
ly c
orre
late
d w
ith M
eteo
rolo
gica
l fac
tors
. The
pat
tern
s obs
erve
d w
ere
cons
iste
nt w
ith w
hat w
e w
ould
exp
ect g
iven
the
ef-
fect
s of c
limat
e on
the
depo
sitio
n, a
bsor
ptio
n, a
nd d
egra
datio
n of
per
sist
ent o
rgan
ic p
ollu
tant
s inc
ludi
ng p
estic
ides
. Som
e of
thes
e po
lluta
nts a
re k
now
n en
docr
ine
disr
upto
rs a
nd h
ave
been
as
soci
ated
with
pro
stat
e ca
ncer
.
Ban
d et
al.,
(201
1)C
anad
a1,
516
4,99
4D
DT
OR
= 1
.68
(95%
CI =
1.0
4 - 2
.70)
/Sim
azin
e O
R =
1.8
9 (9
5% C
I = 1
.08
- 3.3
3)
Lind
ane
OR
= 2
.02
(95%
CI =
1.1
5 - 3
.55)
Expo
sure
to sp
ecifi
c ac
tive
com
poun
ds in
pes
ticid
e w
ith p
rost
ate
canc
er p
atie
nts a
nd a
ge-m
atch
ed in
tern
al c
ontro
ls T
he si
gnifi
cant
ass
ocia
tion
betw
een
pros
tate
can
cer r
isk
and
high
exp
o-su
re to
DD
T, s
imaz
ine,
and
lind
ane
supp
orts
pre
viou
s rep
orts
in th
e lit
erat
ure.
Bar
ry e
t al.,
(201
1)
USA
776
1,44
4A
mon
g m
en w
ith C
T/TT
gen
otyp
es fo
r rs1
9831
32, F
onof
os e
xpos
ure
was
ass
ocia
ted
with
a m
onot
onic
in
crea
se in
pro
stat
e ca
ncer
risk
: low
& h
igh
use
OR
=1.6
5 (0
.91,
3.0
1) a
nd n
o us
e O
R=
3.25
(1.7
8, 5
.92)
.B
ecau
se b
ase
exci
sion
repa
ir (B
ER) i
s the
pre
dom
inan
t pat
hway
invo
lved
in re
pairi
ng o
xida
tive
dam
age,
the
rese
arch
ers e
valu
ated
inte
ract
ions
bet
wee
n 39
pes
ticid
es a
nd 3
94 ta
g si
ngle
-nu
cleo
tide
poly
mor
phis
ms (
SNPs
) for
31
BER
gen
es a
mon
g 77
6 pr
osta
te c
ance
r cas
es a
nd 1
,444
mal
e co
ntro
ls in
a n
este
d ca
se-c
ontro
l stu
dy o
f whi
te A
gric
ultu
ral H
ealth
Stu
dy (A
HS)
pe
stic
ide
appl
icat
ors.
The
sign
ifica
nt fi
ndin
g re
gard
ing
fono
fos i
s con
sist
ent w
ith p
revi
ous A
HS
findi
ngs o
f inc
reas
ed p
rost
ate
canc
er ri
sk w
ith fo
nofo
s exp
osur
e am
ong
thos
e w
ith a
fam
ily
hist
ory
of p
rost
ate
canc
er.
Bur
ns E
t al.,
(201
1)U
SAC
ohor
t12
56 (S
IR =
0.7
4, 9
5% C
I 0.5
7–0.
94).
The
rese
arch
ers m
atch
ed a
n ex
istin
g co
hort
of h
erbi
cide
2,4
-D m
anuf
actu
ring
empl
oyee
s with
can
cer r
egis
tries
in th
ree
US
stat
es re
sulti
ng in
244
can
cers
com
pare
d to
276
exp
ecte
d ca
ses.
Ris
k es
timat
es w
ere
high
er in
the
uppe
r cum
ulat
ive
expo
sure
and
dur
atio
n su
bgro
ups,
yet n
ot st
atis
tical
ly si
gnifi
cant
. Ove
rall,
few
er p
rost
ate
canc
er c
ases
wer
e ob
serv
ed th
an
expe
cted
.
Kou
tros e
t al.,
(201
1)U
SA77
614
44PC
a ris
k (O
R=3
.7, 9
5% C
I: 1.
9-7.
3). n
o pe
trole
um/(O
R=1
.9, 9
5% C
I: 1.
1-3.
2, P
inte
ract
ion=
0.01
; pet
role
um
oil O
R=2
.1, 9
5% C
I: 1.
1-4.
0, P
inte
ract
ion=
0.01
), pe
trole
um d
istil
late
(OR
=3.0
, 95%
CI:
1.5-
6.0,
P in
tera
ctio
n=2.
0x10
(-3))
The
auth
ors e
valu
ated
pes
ticid
e-SN
P in
tera
ctio
ns b
etw
een
45 p
estic
ides
and
191
3 X
ME
SNPs
with
resp
ect t
o pr
osta
te c
ance
r in
the A
gric
ultu
ral H
ealth
Stu
dy.
The
inve
stig
ator
s obs
erve
d se
vera
l pes
ticid
e-SN
P in
tera
ctio
ns in
oxi
dativ
e st
ress
and
pha
se I/
II e
nzym
e ge
nes a
nd ri
sk o
f pro
stat
e ca
ncer
. Add
ition
al w
ork
is n
eede
d to
exp
lain
the
join
t co
ntrib
utio
n of
gen
etic
var
iatio
n in
XM
Es, p
estic
ide
use,
and
pro
stat
e ca
ncer
risk
.
Coc
kbur
n et
al.,
(201
1)U
SA17
316
2m
ethy
l bro
mid
e O
R=
1.62
, (95
% C
I= 1
.02-
2.5
9)an
d a
grou
p of
org
anoc
hlor
ines
OR
=1.6
4, (9
5% C
I= 1
.02,
2.6
3)In
a p
opul
atio
n-ba
sed
case
-con
trol s
tudy
in C
alifo
rnia
’s in
tens
ely
agric
ultu
ral C
entra
l Val
ley
(200
5–20
06),
the
auth
ors i
nves
tigat
ed re
latio
ns b
etw
een
envi
ronm
enta
l pes
ticid
e/fu
ngic
ide
expo
sure
and
pro
stat
e ca
ncer
. In
com
paris
on w
ith u
nexp
osed
per
sons
, inc
reas
ed ri
sks o
f pro
stat
e ca
ncer
wer
e ob
serv
ed a
mon
g pe
rson
s exp
osed
to c
ompo
unds
whi
ch m
ay h
ave
pros
tate
-sp
ecifi
c bi
olog
ic e
ffect
s but
not
am
ong
thos
e ex
pose
d to
oth
er c
ompo
unds
that
wer
e in
clud
ed a
s con
trols
(sim
azin
e, m
aneb
, and
par
aqua
t dic
hlor
ide)
. Thi
s stu
dy p
rovi
des e
vide
nce
of a
n as
soci
atio
n be
twee
n pr
osta
te c
ance
r and
am
bien
t pes
ticid
e ex
posu
res i
n an
d ar
ound
hom
es in
inte
nsel
y ag
ricul
tura
l are
as. T
he a
ssoc
iatio
ns a
ppea
r spe
cific
to c
ompo
unds
with
a p
laus
ible
bi
olog
ic ro
le in
pro
stat
e ca
rcin
ogen
esis
.
Bar
ry, e
t al.,
(201
2)U
SA77
614
44Va
riant
A a
llele
OR
=2.9
8; (9
5% C
I 1.6
5–5.
39) P
inte
ract
5 3
.6 3
102
4; F
DR
-adj
uste
d P
5 0.
11].
Wild
-type
gen
otyp
e (O
R 2
.01;
95%
CI 1
.31–
3.10
for r
s117
4459
6; P
inte
ract
5 7
.2 3
102
4; F
DR
-adj
uste
d P
5 0.
09).
This
arti
cle
inve
stig
ates
inte
ract
ions
bet
wee
n pe
stic
ide
expo
sure
and
324
sing
le-n
ucle
otid
e po
lym
orph
ism
s (SN
Ps) t
aggi
ng 2
7 N
ER g
enes
am
ong
pros
tate
can
cer c
ases
and
mal
e co
ntro
ls in
a
nest
ed c
ase–
cont
rol s
tudy
of w
hite
Agr
icul
tura
l Hea
lth S
tudy
pes
ticid
e ap
plic
ator
s. O
f the
17
inte
ract
ions
that
met
FD
R <
0.2,
3 d
ispl
ayed
a m
onot
onic
incr
ease
in p
rost
ate
canc
er ri
sk w
ith
incr
easi
ng e
xpos
ure
in o
ne g
enot
ype
grou
p an
d no
sign
ifica
nt a
ssoc
iatio
n in
the
othe
r gro
up. M
en c
arry
ing
the
varia
nt A
alle
le a
t ER
CC
1 rs
2298
881
exhi
bite
d in
crea
sed
pros
tate
can
cer r
isk
with
hig
h ve
rsus
no
fonf
os u
se. M
en c
arry
ing
the
varia
nt A
alle
le a
t ER
CC
1 rs
2298
881
exhi
bite
d in
crea
sed
pros
tate
can
cer r
isk
with
hig
h ve
rsus
no
fono
fos u
se. M
en c
arry
ing
the
hom
ozy-
gous
wild
-type
TT
geno
type
at t
wo
corr
elat
ed C
DK
7 SN
Ps, r
s117
4459
6 an
d rs
2932
778
(r2
5 1.
0), e
xhib
ited
incr
ease
d ris
k w
ith h
igh
vers
us n
o ca
rbof
uran
use
. Whi
le re
quiri
ng re
plic
atio
n,
thes
e fin
ding
s sug
gest
a ro
le fo
r NER
gen
etic
var
iatio
n in
pes
ticid
e-as
soci
ated
pro
stat
e ca
ncer
risk
.
Glenn Doolan et al
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014510
physical activity, perceived physical workloads, sedentary work and standing work. Table 4 summarizes reports that investigated ergonomic risk factors for prostate cancer. Past research has mainly focused on physical activity in the workplace. MacLennan et al. (2002) investigated the physical activity of company employees and Lagiou et al. (2008) examined the association of occupational physical activity with the risk of prostate cancer. The association with physical activity tended to be more pronounced for men aged 65 years or younger. Both research teams advised that preventive measures should focus on increasing physical activity. Strom et al. (2008) in analysis stratified by cancer stage, concluded that cases with organ-confined prostate cancer were 56% less likely to have moderate /high levels of occupational physical activity. In a cancer registry study, Flinton and Walters (2004) reported an elevated risk for working subjects with low levels of physical activity compared with a high activity group. They also reported the retired group to have a slightly elevated risk, although it was not statistically significant. This study suggested that physical activity might offer a small but significant reduction in prostate cancer risk for currently employed workers. A Canadian study, Friedenreich et al. (2004) investigated types of physical activity and reported that risks were decreased for occupational and recreational activity but were increased for household activity when comparing the highest and lowest quartiles. For physical activity performed throughout life, only that activity done during the first 18 years of life was associated with decreased risk. When the intensity of activity was examined (i.e., low, <3; moderate, 3-6; and vigorous, >6 metabolic equivalents) only vigorous activity was associated with decreased prostate cancer risk. This study provided inconsistent evidence for an inverse association between physical activity and prostate cancer. This is supported recently by Orsini et al. (2009) who concluded that not sitting for most of the time at work is associated with reduced incidence of prostate cancer. However, Krishnadsan et al. (2007) reported that radiation workers were associated with a higher incidence of prostate cancer as opposed to aerospace workers who have higher activity levels at work which are also invariably associated with prostate cancer. Young et al. (2009) in a systematic review on the risk of prostate cancer from whole body vibration (WBV) exposure related occupations and estimated a combined meta-rate ratio from a systematic review of five case-control and three cohort studies published between 1996 and 2004. A random effects model gave an overall pooled RR estimate of 1.14 (95%CI 0.99-1.30) based on 17 estimates of RR from the eight studies. Significant heterogeneity was found and it was concluded that the non-statistically significant increased pooled RR for prostate cancer obtained from this meta-analysis indicated that occupational exposure to WBV could not be ruled out as a possible risk factor for the disease. This conclusion is not supported by the data. All the studies included in the meta-analysis involved driving occupations that exposed participants to other risk factors such as PAHs, lack of exercise and obesity that could not be controlled
for in the analysis. The non-significant point estimate is, thus, likely to be due to residual confounding. Any future epidemiological studies on this topic need to take these issues seriously in the research design and conduct. A population-based case-control study of men in Northeastern Ontario, Canada, failed to provide evidence for significant occupational risk factors for prostate cancer (Sass-Kortsak et al., 2007) but the authors persisted in their view that whole body vibration exposures and physical activity were worth pursuing in future occupational studies.
Physical and environmental factors Table 5A which summarises relevant reviews and Table 5B which summarises relevant studies, investigating physical and environmental factors that include heat, ionizing radiation, low frequency electromagnetic fields (hence-forth to be referred to as electromagnetic fields (EMF)), radio frequency, and ultraviolet radiation. Our literature search found no reports of studies that implicated either heat or radio frequency radiation with prostate cancer risk. A recent meta-analysis of 11 epidemiological studies of nuclear power plant workers (Park et al., 2010) assessed the relationship between low doses of external ionizing radiation and the risk of cancer mortality. Significant decreased deaths from all cancers except prostate cancer were reported. The authors concluded that further studies were needed to clarify the low SMR of cancers, for which there is no useful screening tool for nuclear power plant workers. A further investigation by Beal et al. (2005) reported that prostate cancer incidence was associated with working in the storage device facilities/within the facility’s laboratories, but employee mortality was lower than expected. Krishnadasan et al. (2007) also suggested that radiation workers compared with aerospace workers were at increased risk of prostate cancer and this was possibly related to lower levels of physical activity. Atkinson et al. (2007) re-assessed early epidemiological studies of the UKAEA workforce that had followed up the mortality of those who worked to the end of 1979, and had reported a significant excess of prostate cancer deaths in some subsets of the cohort, particularly workers internally monitored for tritium contamination and those employed at the Winfrith laboratories. The excess seemed to have been associated with work involving heavy-water reactors. The finding of lower prostate cancer mortality levels during later observational periods led them to conclude that the early findings may have been related to chance.Two recent reviews have investigated cosmic ionizing radiation and risk of prostate cancer (Buja et al., 2005; Ott and Huber, 2006). Ott and Huber, (2006) reviewed 20 studies in detail, 14 retrospective, 3 prospective cohort studies and 3 meta-analyses. Sixteen studies were set in the civil aviation environment, two in the military aviation environment and two in both environments. Three studies reported increased risks for pilots to develop prostate cancer but there was insufficient evidence to support the hypothesis that cosmic radiation might be the causative agent.
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Table 4. Ergonomic Studies
StudyCountry
Cases(N)
Controls(N)
Findings OR(95%CI) Summary
MacLennan et al., (2002)
USA
46 obs.40 exp.
1999 PCa 11/6.3 (SIR=175, CI = 87-312)A/Workers 5/1.3 (SIR=394, CI=128-920) C/Workers 6/8.0 3 (SIR=119, CI=44-260)
In a study on atrazine and other triazine herbicides, of the 11 prostate cancer cases, nine were diag-nosed at an early clinical stage. Indicates no causal relationship between atrazine and PCa.
Flinton & Walters (2004)Ireland
3,008 15,737 High Activity level OR = 2.13, (95%CI = 1.29 - 3.52)
An investigation into physical activity and prostate cancer. Despite limitations in the data, an elevated risk was seen in working subjects with low levels of activity compared with the high activity group. In the retired group there was a slight elevation of risk, although it was not statisti-cally significant. The study suggests that physical activity offers a small but significant reduction in prostate cancer risk for those people in work.
Friedenreich et al., (2004)
Canada
988 1,063 OA OR=0.90 (95% CI = 0.66 - 1.22) FEYL OR = 0.78 (95% CI = 0.59 -1.04)VA OR=0.70 (95%CI=0.54-0.92)
No association for total lifetime physical activity and prostate cancer risk was reported. The risks were decreased for Occupational Activity (OA) but were increased for household activity when comparing the highest and lowest quartiles. For activity performed at different age periods through-out life, activity done during the First 18 years of Life (FEYL) decreased risk. Vigorous activity decreased prostate cancer risk.
Sass-Kortsak et al., (2007)
Canada
760 1,632 LCOPA OR = 1.33 (95% CI = 1.02 - 1.74)WBV OR = 1.38 (95% CI = 1.07 - 1.78)
This study does not provide strong evidence for significant occupational risk factors for prostate cancer. Whole-body vibration (WBV) exposures, as well as physical activity (PA), may be worth pursuing in future occupational studies. Physical Activity (LCOPA) was reported to have a signifi-cant odds ratio.
Lagiou et al.,( 2008)
Greece
PCa 320BPH 184
246 High versus low activity for PCa OR=0.69 (95%CI=0.40-1.22)BPH OR=0.59 (95%CI =0.31-1.11)
There was a suggestive inverse association of physical activity with prostate cancer (P for trend 0.12) and a significant one with BPH (P for trend 0.04. The association of physical activity with both conditions tended to be more pronounced among men 65 years old or younger.
Strom et al., (2008)
USA
176 174 OPA OR=0.44 (95%CI=0.26-0.76)Obesity OR=2.50 (95%CI=1.20-5.20)
Compared to controls, cases were three times more likely to work in jobs with high agrichemical exposure, and 54% less likely to work in jobs with moderate/high occupational physical activity. Increased risk of being diagnosed with advanced PCa was associated with obesity at the time, but not with occupational physical activity.
Krishnadasan et al., (2008)
USA
362 1,805 ASW OR=0.55 (95%CI=0.32-0.95)RW OR=0.95 (95%CI=0.43-2.1)
Investigating occupational physical activity and prostate-cancer incidence among workers at a nuclear and rocket engine-testing facility in Southern California. High activity levels at work were inversely associated with prostate-cancer incidence among aerospace workers (ASW), but not among radiation workers (RW). The results suggest that adult men who are more continually active at work may have a decreased risk of prostate cancer.
Orsini et al., (2009)
Sweden
Fatal=190Incidence=2,735
Total Cohort
=45,887
Men who sit half of the time at work experienced a 20% lower risk (95% CI: 7–31%).
The possible benefit of lifetime physical activity (PA) in reducing prostate cancer incidence and mortality is unclear. This prospective cohort of 45 887 men aged 45–79 years was followed up from January 1998 to December 2007 for prostate cancer incidence (n: 2735) and to December 2006 for its subtypes and for fatal (n: 190) prostate cancer. Multivariate-adjusted incidence in the top quartile of lifetime total Physical Activity decreased by 16% (95% confidence interval (CI): 2–27%) compared with that in the bottom quartile. It was also observed that an inverse association between average lifetime work or occupational activity and walking or bicycling duration and prostate cancer risk for advanced prostate cancer for every 30 min per day increment of lifetime walking or bicycling in the range of 30 to 120 min per day. These results suggest that not sitting for most of the time during work or occupational activity and walking or bicycling more than 30 minutes per day during adult life is associated with reduced incidence of prostate cancer.
Buja et al. (2005) performed a meta-analysis of cosmic rays and prostate cancer risk using a random effect model for 9 cohort studies on pilots and male flight attendants. For civil pilots the meta-SIR was 1.47 (1.06-2.05) for prostate cancer. They suggested that non-occupational risk factors such as age (civil pilots are older than military pilots and cabin attendants) and disrupted sleep pattern (entailing hyposecretion of melatonin, which has been reported to suppress proliferative effects of androgen on prostate cancer cells) might be involved. Previously, an investigation of cosmic rays and risk of prostate cancer for airline pilots reported an association with the number of long distance flights (Pukkala et al., 2002), but the authors stressed that the finding needed to be confirmed and queried whether this association could be confounded by sexual activity or other factors, such as time spent in unusual locations. When looking at the reported risk in relation to diagnostic radiation procedures and the risk of prostate cancer, Myles et al. (2008) reported a risk to patients undergoing barium enema and hip x-rays at the 5 year interval and with those with a family history, at the 20 year interval, the adjusted odds ratio for hip x-rays was 5.01 (95%CL=0.36-3.43) at the ten year interval and 14.23 (95%CL=0.53-4.02) at the 20 year interval. Unfortunately there was no reported adjustment for age. In relation to occupational exposure to radiation in treating physicians (Schiefer et al., 2009) in the seeding of the prostate,
the cumulative effect of treatment applications on the physician was such that experienced physicians could undertake 400 applications per year without exceeding the threshold value, but inexperienced physicians could only safely undertake 200 applications per year. This study had too small a sample to give more definitive associations regarding prostate cancer and occupational radiation exposure in the physicians themselves.
Electro-Magnetic Fields A nested case-control study of US electricity utility workers investigated a possible association between exposure to electromagnetic fields or polychlorinated biphenyls (PCBs) and mortality from prostate cancer (Charles et al., 2003). It reported that workers categorized in the highest decile of EMF exposure were twice as likely to die from prostate cancer as those in lower deciles of exposure to EMFs, following adjustment for PCB exposure, race, and active work status within the past 2 years. Exposure to high levels of both EMFs and PCBs was not associated with prostate cancer mortality. They concluded that the possible association between EMF exposure and prostate cancer mortality warranted further investigation.
Ultraviolet Radiation Evidence from various studies using different experimental approaches has been interpreted as showing
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Table 5A. Physical and Environmental Reviews and StudiesReviewsCountry
Cases(N)
Controls(N)
FindingsOR(95%CI)
Summary
Buja et al., (2005)Italy
meta-analysis Male cabin attendants & civil and military pilots, meta-SIRs were 3.42 (CI = 1.94-6.06).In civil pilots, meta-SIR was 1.47 (1.06-2.05) for prostate cancer.
Flight personnel are exposed to cosmic ionizing radiation, chemicals (fuel, jet engine exhausts, cabin air pollutants), electromagnetic fields from cockpit instruments, and disrupted sleep patterns.. These tumours share as risk factors, ionizing radiation, recreational sun exposure and socioeconomic status. The meta-SIRs are not adjusted for confounding; the magnitude of risk for melanoma decreased when we corrected for socioeconomic status. Age (civil pilots are older than military pilots and cabin attendants) and disrupted sleep pattern (entailing hyposecretion of melatonin, which has been reported to suppress proliferative effects of androgen on prostate cancer cells) might be involved.
Moon et al., (2005)UK
Review No Meta-Analysis Collectively, these data suggest the hypothesis that, UVR exposure has beneficial effects on susceptibility and outcome to a variety of complex diseases including PCa. We describe evidence from studies in various diseases, but mainly from prostate cancer patients, that supports this hypothesis, but we emphasize that, although supportive data are avail-able, the concept is unproven. Indeed, other explanations are possible. However, given the potentially important public health implications of the hypothesis and the potential for the development of novel therapeutic modalities, we believe the concept is worthy of further investigation.
Ott & Huber, (2006)Switzer-land
Review of 20 studies 1990 - 2003.
1 retro-/prospective13 retrospective
3 prospective cohort3 meta-analysis studies
Seven out of nine studies reported an identical or decreased over-all-risk for aviators to develop cancer of any kind compared to the general population. Three studies reported an increased risk for the development of prostate cancer.
Sixteen studies were set in the civil aviation environment, two studies in the military aviation environment and two studies were set in both environments.. Although this review reported some studies that identified higher risks for pilots to develop cancer of the skin, prostate cancer or leukaemia, there is not enough scientific evidence to support the hypoth-esis, that cosmic radiation is the cause for these findings. It shows to be important to include other factors in the interpretation of the results, since some of the findings may be well explained by life-style factors of the aviation community.
Young et al., (2009)Canada
systematic review and meta-analysis
The overall pooled RR estimate was 1.14 (95% CI 0.99-1.30) for the random effects model, based on 17 estimates of relative risk from the eight studies. Significant heterogeneity was reported.
The risk of prostate cancer in whole body vibration was estimated in re-lated occupations and a combined meta-rate ratio. Five case-control and three cohort studies published between 1996 and 2004 were analysed. There was no indication of publication bias. The increased, though not statistically significant pooled RR for prostate cancer obtained in this meta-analysis indicates that occupational exposure to WBV cannot be ruled out as a possible risk factor for the disease. However, all included studies involved driving occupations with exposure to other risk factors for prostate cancer. Therefore, further epidemiologic studies are needed to better understand this association.
that, apart from harmful effects on the pathogenesis of the common skin cancers, ultraviolet radiation (UVR) might exert a beneficial effect on development of various internal cancers and other chronic diseases. Moon et al. (2005) describe evidence from studies investigating various diseases, including prostate cancer, that supports a beneficial effect of UVR, but they emphasize that the concept is yet to be convincingly established but worthy of further investigation. Other researchers such as Freedman et al. (2002) have supported this position and reported residential and occupational exposure to sunlight to be negatively and significantly associated with mortality from female breast, ovarian, prostate, and colon cancer. Bodiwala et al. (2003a) identified a combination of exposure parameters to UVR that distinguished prostate cancer patients from those with BPH. This study, however, did not investigate UVR exposure related to occupation, but a review of previously unpublished data (Bodiwala et al., 2003b) confirmed that high levels of cumulative UVR exposure, adult sunbathing, childhood sunburns and regular holidays in hot climates were each independently and significantly associated with a reduced risk of prostate cancer. Others (de Vries et al., 2007) also reported UVR exposure to significantly decrease the risk of advanced prostate cancer, indicating a possible anti-progression effect of UVR. Patients with a skin cancer on the chronically UVR exposed head and neck area and those diagnosed after the age of 60 years had decreased prostate cancer incidence rates. These results support
the hypothesis that UVR exposure might protect against prostate cancer.
Psychosocial factors In occupational exposure research Workload refers to an individual’s workload as they perceive it. The question arises whether a worker who believes they have had a high or onerous workload over a number of years is likely to develop the disease under investigation. This includes workers who admit to continuously working more than fifty hours a week over more than twelve months at a time. The hypothesis is that associated stress over a number of years or decades could influence risk. No recent literature was identified on this exposure and prostate cancer.
Conclusions
IARC classifies the heavy or toxic metals including lead, cadmium, hexavalent chromium compounds and arsenic as carcinogenic. Blood levels of zinc and selenium and their ratio to cadmium levels seem to be intricately entwined and may point to aggressive prostate cancer diagnosis in the future, but these links require further clarification. Evidence concerning risks related to chemical exposures such as hydrocarbon solvents and pesticides remains unconvincing. Although the evidence for PAHs and PCBs is stronger, there are many specific pesticide agents that have not been significantly associated with prostate cancer. Further research to clarify the
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hypothesis of acquired apoptotic resistance in relation to cadmium exposure whereby the body’s ability to kill off cancer cells is inhibited also needs to be clarified and tested on males.
Recent investigations of ergonomic risk factors showed high levels of occupational activity level to be beneficial and low levels to be modestly positively associated with prostate cancer risk. The association was stronger in the presence of a family history of prostate cancer which is known to be a significant risk factor and, thus, a possible confounding factor. Whole body vibration was also implicated in two articles related to physical activity, but further research on male workers will require cohort studies to provide firm evidence.
In relation to physical or environmental risk factors, for ionizing radiation all three reviews since 2002 (Buja et al., 2005; Ott and Huber 2006; Park et al., 2010) agree that there is insufficient evidence to support a relationship between ionizing radiation exposure and prostate cancer, but none could rule out the possibility of a very small risk. Several reports implicate UVR as being protective against PC. It was also concluded (Buja et al., 2005) that there were too many confounders such as age, disrupted
sleep patterns, long distance flights and unusual stopovers and the presence of such factors require to be further investigated. EMFs were reported to be related to high mortality rates for US utility workers at high exposure levels compared with lower exposure levels, but overall the mortality levels were not significantly different to unity.
Three recent reviews of pesticides and prostate cancer suggested that reported risk levels were too low to significantly implicate pesticides, although modest effects associated with pesticides could not be excluded. The major limitation of these reviews is they tend to target a single specific agent, not the full range of possible agents and few attempt to address mixtures and co-carcinogens. Unfortunately, no major reviews have been published regarding low occupational physical activity simply due to the lack of publications on this topic. Methodological difficulties in occupational and non occupational exposure to UVR have resulted in a limited number of studies investigating occupational UVR exposure and prostate cancer.
The major limitation of the occupational literature is the lack of prospective cohort studies in most areas
Table 5B. Physical and Environmental StudiesReviewsCountry
Cases(N)
Controls(N)
FindingsOR(95%CI)
Summary
Freedman et al., (2002)USA
sunlight OR = 0.82 (95%CI=0.70-0.97) An investigation into mortality from prostate cancer. Residential exposure to sunlight was negatively and significantly associated with mortality from prostate cancer.
Gershkevitsh et al., (2002)Germany
6 3 Observational Human laboratory study Studying the analysis of blood samples in relation to Chromosomal aberration in peripheral lymphocytes and doses to the active bone marrow in radiotherapy of prostate cancer.
Bodiwala et al., (2003)
UK
PCa 453 BPH 312
78.7% increase in scores (<30)40% increase in scores (>8)
Cohort study of two cohorts of PCa & BPH of self reported exposure. Low sunlight exposure confers increased prostate cancer risk. This study did not look at occupational exposure.
Bodiwala et al., (2003)
UK
PCa 212 BPH 135
Decreased level sunbathing 5 times x PCa Risk
A confirmatory study. Exposure to ultraviolet (UV) radiation may be protective to prostate cancer. It was confirmed that higher levels of cumulative exposure such as adult sunbathing and childhood sunburns and regular holidays in hot climates were each independently and significantly associated with a reduced risk of this cancer.
Pukkala et al., (2002)Finland
466 10,051 There was an increase in the relative risk of prostate cancer with increasing number of flight hours in long-distance aircraft (p trend 0.01).
Based on a cohort of 138,405 air craft workers. Work-related factors affect cancer pattern of the pilots. A cohort of 10,051 male and 160 female airline pilots from Denmark, Finland, Iceland, Norway, and Sweden was followed for cancer incidence through the national cancer registries. It did not indicate a marked increase in cancer risk attributable to cosmic radiation.
Charles et al., (2003)USA
387 1935 EMFs OR=2.02, 95%CI=1.34-3.04)PCBs OR=1.47 (95%CI=0.97-2.24)Non-White OR = 3.67 (95%CI=2.66-5.06)
Investigated EMFs and PCBs and mortality from prostate cancer among US electric utility workers. Workers categorized in the highest 10 percent of EMF exposure were twice as likely to die from prostate cancer as those exposed to EMFs at lower levels. Exposure to high levels of both EMFs and PCBs showed no association with prostate cancer mortality. Non-White race was strongly associated with risk of prostate cancer mortality. The association between EMF exposure and prostate cancer mortality warrants further investigation.
Atkinson et al., (2007)
England
475 39,546 Comparison of two data sets 1946-1979 and 1980 -1997.
Confirmed the 2004 results by the same authors in the workforce of the UK Atomic Energy Authority (UKAEA). The association of prostatic cancer with radiation dose was much less significant than in previous reports. Overall, radiation workers at UKAEA showed no excess mortality. The previously detected association of prostate cancer with high radiation dose may have been a statistical artifact or a risk associated with discontinued activities.
Beall et al., (2005)USA
6,579 120,257 Exp. deaths SMR=65 (95%CI=64-67)PCa SMR=198 (95%CI=117-313)
Cohort study of mortality with 6,579 observed deaths, for all cancers combined (2159 observed) and for other major diseases. Prostate cancer was associated with facilities/laboratories at the storage device facility.
de Vries et al., (2007)
Holland
13,541 CPa SIR=0.89 (95%CI=0.78-0.99)ACPa SIR=0.73 (95%CI=0.56-0.94)
Cohort study in which skin cancer patients were at decreased risk of developing prostate cancer compared with the general population especially shortly after diagnosis. The risk of advanced prostate cancer (APCa) was significantly decreased indicating a possible anti-progression effect of UVR. UVR protects against PCa.
Myles,, et al., (2008)
UK
431 409 Hip x-rays 5yrs adj. OR=2.23 (95%CI=1.42-3.49)adjusted for family history of cancer, 10yrs adj. OR=5.01(95%CI=1.64-15.31)20yrs adj. OR 14.23(95%CI=1.83-110.74)
A case-control study to investigate whether exposure to low dose ionisation radiation from diagnostic x-ray procedures could be established as a risk factor for prostate cancer. For those with a family history of cancer, exposures to hip x-rays dating 10 or 20 years before diagnosis were associated with a significantly increased risk of prostate cancer: Findings show that exposure of the prostate gland to diagnostic radiological procedures may be associated with increased cancer risk. This effect possibly modified by a positive family history of cancer which suggests that genetic factors may play a role.
Schiefer et al., (2009)
Australia
4 Doctors plus24 Patients
Radiation exposure of the treating physician during prostate seed implantation. If no other radiation exposure needs to be considered, an experienced physician can perform about 400 applications per year without exceeding the limit of 500mSv/year; for novices, the corre-sponding figure is about 200.
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reviewed. The results are inconsistent from study to study and generally this is due to the reliance upon the lack of homogeneity of the case-control studies and prevalence (ecological) studies. Exposure assessment bias is a recurring limitation of many of the studies in this review, primarily due to the poor exposure assessment methodology. Many past studies have relied upon occupation or industry to describe exposure, with only a few studies using Job Exposure Matrices (JEMs) or expert assessment. Occasionally, marginally significant results are attributed to chance and significant results attributed to age or genetics. A limitation suggested by Macfarlane et al. (2009) is that the job title of “farm worker” is a poor surrogate exposure metric for pesticides, herbicides or insecticides, with serious misclassification potential for level and duration of exposure. Future studies must improve exposure assessment methodology for more meaningful results.
References
Achanzar WE, Diwan BA, Liu J, et al (2001). Cadmium-induced malignant transformation of human prostate epithelial cells. Cancer Res, 61, 455-8.
Achanzar WE, Webber MM, Waalkes MP (2002). Altered apoptotic gene expression and acquired apoptotic resistance in cadmium-transformed human prostate epithelial cells. Prostate, 52, 236-44.
Agalliu I, Eisen EA, Kriebel D, Quinn MM, Wegman DH (2005). A biological approach to characterizing exposure to metalworking fluids and risk of prostate cancer (United States). Cancer Causes Control, 16, 323-31.
Agalliu I, Kriebel D, Quinn MM, Wegman DH, Eisen EA (2005). Prostate cancer incidence in relation to time windows of exposure to metalworking fluids in the auto industry. Epidemiology, 16, 664-71.
Anetor JI, Ajose F, Anetor GO, et al (2008). High cadmium/zinc ratio in cigarette smokers: potential implications as a biomarker of risk of prostate cancer. Niger J Physiol Sci, 23, 41-9.
Aronson KJ, Wilson JW, Hamel M, et al (2010). Plasma organochlorine levels and prostate cancer risk. J Exposure Sci & Environ Epidemiol, 20, 434-45.
Atkinson WD, Law DV, Bromley KJ, et al (2007). A decline in mortality from prostate cancer in the uk atomic energy authority workforce. J Radiolog Protection, 27, 437-45.
Band PR, Abanto Z, Bert J, et al (2011). Prostate cancer risk and exposure to pesticides in British Columbia farmers. Prostate, 71, 168-83.
Barry KH, Koutros S, Andreotti G, et al (2012). Genetic variation in nucleotide excision repair pathway genes, pesticide exposure and prostate cancer risk. Carcinogenesis, 33, 331-7.
Barry KH, Koutros S, Berndt SI, et al (2011). Genetic variation in base excision repair pathway genes, pesticide exposure, and prostate cancer risk. Environ Health Perspect, 119, 1726-32.
Beall C, Bender TJ, Cheng H, et al (2005). Mortality among semiconductor and storage device-manufacturing workers. J Occup Environ Med, 47, 996-1014.
Benbrahim-Tallaa L. Waalkes MP (2008). Inorganic arsenic and human prostate cancer. Environ Health Perspect, 116, 158-64.
Bodiwala D, Luscombe CJ, French ME, et al (2003). Associations between prostate cancer susceptibility and parameters of exposure to ultraviolet radiation. Cancer Lett, 200, 141-8.
Bodiwala D, Luscombe CJ, Liu S, et al (2003). Prostate cancer
risk and exposure to ultraviolet radiation: further support for the protective effect of sunlight. Cancer Lett, 192, 145-9.
Boers D, Zeegers MP, Swaen GM, et al (2005). The influence of occupational exposure to pesticides, polycyclic aromatic hydrocarbons, diesel exhaust, metal dust, metal fumes, and mineral oil on prostate cancer: a prospective cohort study. Occup Environ Med, 62, 531-7.
Bostwick DG, Burke HB, Djakiew D, et al (2004). Human prostate cancer risk factors. Cancer, 101, 2371-490.
Budnik LT, Kloth S, Velasco-Garrido, M Baur X (2012). Prostate cancer and toxicity from critical use exemptions of methyl bromide: environmental protection helps protect against human health risks. Environ Health, 11, 5.
Buja A, Lange JH, Perissinotto E, et al (2005). Cancer incidence among male military and civil pilots and flight attendants: an analysis on published data. Toxicol and Indus Health, 21, 273-82.
Burns C, Bodner K, Swaen G, et al (2011). Cancer incidence of 2,4-d production workers. International J of Environmental Res & Public Health, 8, 3579-90.
Charles LE, Loomis D, Shy C (2003). Electromagnetic fields, polychlorinated biphenyls, and prostate cancer mortality in electric utility workers. Am J Epidemiol, 157, 683-91.
Christensen CH, Platz EA, Andreotti G, et al (2010). Coumaphos exposure and incident cancer among male participants in the agricultural health study (AHS). Environ Health Perspect, 118, 92-6.
Cockburn M, Mills P, Zhang X, et al (2011). Prostate cancer and ambient pesticide exposure in agriculturally intensive areas in California. Am J Epidemiol, 173, 1280-8.
Crook JM, O’Callaghan CJ, Duncan G, et al (2012). Intermittent androgen suppression for rising PSA level after radiotherapy. New Engl J Med, 367, 895-903.
Cui JS, Staples MP, Hopper JL, et al (2001). Segregation analysis of 1,476 population-based Australian families affected by prostate cancer. Am J Human Genetics, 68, 1207-18.
De Vries E, Soerjomataram I, Houterman S, Louwman, MW, Coebergh JW (2007). Decreased risk of prostate cancer after skin cancer diagnosis: a protective role of ultraviolet radiation? Am J Epidemiol, 165, 966-72.
Delzell E, Brown DA, Matthews R (2003). Mortality among hourly motor vehicle manufacturing workers. J Occupational & Environmental Medicine, 45, 813-30.
Dennis LK, Dawson DV (2002). Meta-analysis of measures of sexual activity and prostate cancer. Epidemiology, 13, 72-9.
Dombi GW, Rosbolt JP, Severson RK (2010). Neural network analysis of employment history as a risk factor for prostate cancer. Computers in Biology & Medicine, 40, 751-7.
Drasch G, Schopfer J. Schrauzer GN (2005). Selenium/Cadmium ratios in human prostates: indicators of prostate cancer risk of smokers and nonsmokers, and relevance to the cancer protective effects of selenium. Biol Trace Elem Res, 103, 103-7.
Flinton DM, Walters NJ (2004). Occupational activity and risk of prostate cancer in ireland. J Radiotherapy in Practice, 4, 102-6.
Freedman DM, Dosemeci M, Mcglynn K (2002). Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case-control study. Occup Environ Med, 59, 257-62.
Friedenreich CM, Mcgregor SE, Courneya KS, Angyalfi SJ, Elliott FG (2004). Case-Control study of lifetime total physical activity and prostate cancer risk. Am J Epidemiol, 159, 740-9.
Fritschi L, Glass DC, Tabrizi JS, Leavy JE, Ambrosini GL (2007). Occupational risk factors for prostate cancer and benign prostatic hyperplasia: a case–control study in Western
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014 515
DOI:http://dx.doi.org/10.7314/APJCP.2014.15.2.501An Update on Occupation and Prostate Cancer
Australia. Occupational and Environmental Med, 64, 60-5.Gershkevitsh E, Hildebrandt G, Wolf U, et al (2002).
Chromosomal aberration in peripheral lymphocytes and doses to the active bone marrow in radiotherapy of prostate cancer. Strahlentherapie und Onkologie, 178, 36-42.
Giles GG, Severi G, English DR, et al (2003). Early growth, adult body size and prostate cancer risk. Int J Cancer, 103, 241-5.
Giles GG, Severi G, Mccredie MR (2001). Smoking and prostate cancer: findings from an Australian case-control study. Ann Oncol, 12, 761-5.
Girschik J, Glass D, Ambrosini GL, Fritschi L (2010). Could mining be protective against prostate cancer? A study and literature review. Occupational & Environmental Med, 67, 365-74.
Goyer RA, Liu J, Waalkes MP (2004). Cadmium and cancer of prostate and testis. Biometals, 17, 555-8.
Gwini S, Macfarlane E, Del Monaco A, et al (2012). Cancer incidence, mortality, and blood lead levels among workers exposed to inorganic lead. Ann Epidemiol, 22, 270-6.
Hauptmann M, Lubin JH, Stewart PA, Hayes RB, Blair A (2004). Mortality from solid cancers among workers in formaldehyde industries]. Am J Epidemiol, 159, 1117-30.
Hessel PA, Kalmes R, Smith TJ (2004). A nested case-control study of prostate cancer and atrazine exposure. J Occup Environ Med, 46, 379-85.
Huff J, Lunn RM, Waalkes MP, Tomatis L, Infante PF (2007). Cadmium-induced cancers in animals and in humans. Int J Occupational & Environ Health, 13, 202-12.
IARC working group (2012). Arsenic, metals, fibres, and dusts. IARC monographs on the evaluation of carcinogenic risks to humans. IARC, 100, 11-465,
Klaassen CD, Amdur MO, Doull J (1996). Casarett and Doull’s Toxicology The Basic Science of Poisons, New York ; London, Mcgraw-Hill, Health Professions Division.
Koutros S, Alavanja MC, Lubin JH (2010). An update of cancer incidence in the agricultural health study. J Occupational & Environ Med, 52, 1098-105.
Koutros S, Beane Freeman E, Berndt SI, et al (2010). Pesticide use modifies the association between genetic variants on chromosome 8q24 and prostate cancer. Cancer Res, 70, 9224-33.
Koutros S, Andreotti G, Berndt SI, et al (2011). Xenobiotic-metabolizing gene variants, pesticide use, and the risk of prostate cancer. Pharmacogenetics and Genomics, 21, 615-23.
Koyama H, Kitoh H, Satoh M, Tohyama C (2002). Low dose exposure to cadmium and its health effects (1). Genotoxicity and carcinogenicity. Nippon Eiseigaku Zasshi, 57, 547-55.
Krishnadasan A, Kennedy N, Zhao Y, Morgenstern H, Ritz B (2007). Nested case-control study of occupational chemical exposures and prostate cancer in aerospace and radiation workers. Am J Industrial Med, 50, 383-90.
Kumar V, Yadav CS, Singh S (2010). Cyp 1a1 polymorphism and organochlorine pesticides levels in the etiology of prostate cancer. Chemosphere, 81, 464-8.
Lagiou A, Samoli E, Georgila C, et al (2008). Occupational physical activity in relation with prostate cancer and benign prostatic hyperplasia. Eur J Cancer Prev, 17, 336-9.
Lam TV, Agovino P, Niu X, Roche L (2007). Linkage study of cancer risk among lead-exposed workers in New Jersey. Sci Total Environ, 372, 455-62.
Landau-Ossondo M, Rabia N, Jos-Pelage J (2009). Why pesticides could be a common cause of prostate and breast cancers in the french caribbean island, martinique. An overview on key mechanisms of pesticide-induced cancer. Biomedicine & Pharmacotherapy, 63, 383-95.
Lee JD, Wu SM, Lu LY, Yang YT, Jeng SY (2009). Cadmium
concentration and metallothionein expression in prostate cancer and benign prostatic hyperplasia of humans. J Formos Med Assoc, 108, 554-9.
Li Q, Nishijo M, Nakagawa H, et al (2011). Relationship between urinary cadmium and mortality in habitants of a cadmium-polluted area: a 22-year follow-up study in Japan. Chinese Med J, 124, 3504-9.
Lumey LH, Pittman B, Wynder EL (1998). Alcohol use and prostate cancer in U.S. Whites: no association in a confirmatory study. Prostate, 36, 250-5.
Lynch SM, Mahajan R, Beane Freeman LE, Hoppin JA, Alavanja MC (2009). Cancer incidence among pesticide applicators exposed to butylate in the agricultural health study (AHS). Environ Res, 109, 860-8.
Lynch SM, Rusiecki JA, Blair A (2006). Cancer incidence among pesticide applicators exposed to cyanazine in the Agricultural Health Study. Environ Health Perspect, 114, 1248-52.
Macfarlane E, Glass D, Fritschi L (2009). Is farm-related job title an adequate surrogate for pesticide exposure in occupational cancer epidemiology? Occupational & Environ Med, 66, 497-501.
Maclennan PA, Delzell E, Sathiakumar N (2002). Cancer incidence among triazine herbicide manufacturing workers. J Occup Environ Med, 44, 1048-58.
Mahajan R, Blair A, Lynch CF (2006a). Fonofos exposure and cancer incidence in the Agricultural Health Study. Environ Health Perspect, 114, 1838-42.
Mahajan R, Bonner MR, Hoppin JA, Alavanja MC (2006). Phorate exposure and incidence of cancer in the Agricultural Health Study. Environ Health Perspect, 114, 1205-9.
Mills PK, Yang R (2003). Prostate cancer risk in california farm workers. J Occup Environ Med, 45, 249-58.
Mink PJ, Adami HO, Trichopoulos D, Britton NL, Mandel JS (2008). Pesticides and prostate cancer: a review of epidemiologic studies with specific agricultural exposure information. Eur J Cancer Prev, 17, 97-110.
Moon SJ, Fryer AA, Strange RC (2005). Ultraviolet radiation, vitamin d and risk of prostate cancer and other diseases. Photochem Photobiol, 81, 1252-60.
Mullins JK, Loeb S (2012). Environmental exposures and prostate cancer. Urol Oncol, 30, 216-9.
Myles P, Evans S, Lophatananon A, et al (2008). Diagnostic radiation procedures and risk of prostate cancer. Br J Cancer, 98, 1852-6.
Nakamura K, Yasunaga Y, Ko D (2002). Cadmium-induced neoplastic transformation of human prostate epithelial cells. Int J Oncol, 20, 543-7.
Ndong JR, Blanchet P, Multigner L (2009). Pesticides and prostate cancer: epidemiological data. Bull Cancer, 96, 171-80.
Orsini N, Bellocco R, Bottai M, et al (2009). A prospective study of lifetime physical activity and prostate cancer incidence and mortality. Br J Cancer, 101, 1932-8.
Ott C, Huber S (2006). The clinical significance of cosmic radiation in aviation. Praxis, 95, 99-106.
Park ES, Moon K, Kim HN. Lee WJ, Jin YW (2010). Radiation exposure and cancer mortality among nuclear power plant workers: a meta-analysis. J Prev Med Public Health, 43, 185-92.
Platz EA, Helzlsouer K J, Hoffman SC, et al (2002). Prediagnostic toenail cadmium and zinc and subsequent prostate cancer risk. Prostate, 52, 288-96.
Prince MM, Ruder AM, Hein MJ (2006). Mortality and exposure response among 14,458 electrical capacitor manufacturing workers exposed to Polychlorinated Biphenyls (PCBs). Environ Health Perspect, 114, 1508-14.
Prins GS (2008). Endocrine disruptors and prostate cancer risk.
Glenn Doolan et al
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014516
Endocrine-Related Cancer, 15, 649-56.Pukkala E, Aspholm R, Auvinen A, et al (2002). Incidence
of cancer among nordic airline pilots over five decades: occupational cohort study. BMJ, 325, 567.
Pukkala E, Martinsen JI, Lynge E, et al (2009). Occupation and cancer - follow-up of 15 million people in five nordic countries. Acta Oncologica, 48, 646-790.
Ruder AM, Ward EM, Dong M, Okun A, Davis-King K (2004). Mortality patterns among workers exposed to styrene in the reinforced plastic boatbuilding industry: an update. Am J Industrial Med, 45, 165-76.
Rusiecki JA, Hou L, Lee WJ, et al (2006). Cancer incidence among pesticide applicators exposed to metolachlor in the agricultural health study. Int J Cancer, 118, 3118-23.
Rybicki BA, Neslund-Dudas C, Nock NL, et al (2006). Prostate cancer risk from occupational exposure to polycyclic aromatic hydrocarbons interacting with the GSTP1 Ile105Val polymorphism. Cancer Detect Prev, 30, 412-22.
Sahmoun AE, Case LD, Jackson SA, Schwartz GG (2005). Cadmium and prostate cancer: a critical epidemiologic analysis. Cancer Investigation, 23, 256-63.
Sass-Kortsak AM, Purdham JT, Kreiger N, Darlington G, Lightfoot NE (2007). Occupational risk factors for prostate cancer. Am J Ind Med, 50, 568-76.
Sathiakumar N, Maclennan PA, Mandel J, Delzell E (2011). A review of epidemiologic studies of triazine herbicides and cancer. Critical Reviews In Toxicol, 41, 1-34.
Sawada N, Iwasaki M, Inoue M (2010). Plasma organochlorines and subsequent risk of prostate cancer in japanese men: a nested case-control study. Environ Health Perspect, 118, 659-65.
Schiefer H, Von Toggenburg F, Seelentag W, et al (2009). Exposure of treating physician to radiation during prostate brachytherapy using iodine-125 seeds: dose measurements on both hands with thermoluminescence dosimeters. Strahlentherapie Und Onkologie, 185, 689-95.
Settimi L, Masina A, Andrion A, Axelson O (2003). Prostate cancer and exposure to pesticides in agricultural settings. Int J Cancer, 104, 458-61.
Sharma-Wagner S, Chokkalingam AP, Malker HS (2000). Occupation and prostate cancer risk in Sweden. J Occupational & Environ Med, 42, 517-25.
Siddiqui MK, Srivastava S, Mehrotra PK (2002). Environmental exposure to lead as a risk for prostate cancer. Biomed Environ Sci, 15, 298-305.
Singh BR, Singh BN, Khan W, Singh HB, Naqvi AH (2012). Ros-mediated apoptotic cell death in prostate cancer LNCaP cells induced by biosurfactant stabilized CdS quantum dots. Biomaterials, 33, 5753-67.
Soto AM, Sonnenschein C (2010). Environmental causes of cancer: endocrine disruptors as carcinogens. Nature Rev Endocrinology, 6, 363-70.
St-Hilaire S, Mannel S, Commendador A, et al (2010). Correlations between meteorological parameters and prostate cancer. Int J Health Geographics, 9, 19.
Strom SS, Yamamura Y, Flores-Sandoval FN, Pettaway CA, Lopez DS (2008). Prostate cancer in mexican-americans: identification of risk factors. Prostate, 68, 563-70.
Subahir MN, Shah SA, Zainuddin ZM (2009). Risk factors for prostate cancer in universiti kebangsaan malaysia medical centre: a case-control study. Asian Pac J Cancer Prev, 10, 1015-20.
Telisman S, Colak B, Pizent A, Jurasovic J, Cvitkovic P (2007). Reproductive toxicity of low-level lead exposure in men. Environ Res, 105, 256-66.
Thursfield V, Farrugia H (Eds.) (2011). Cancer in Victoria: Statistics & Trends 2010. Cancer Epidemiology Centre,
Cancer Council Victoria.Thursfield V, Farrugia H, Giles G (2011). Cancer in Victoria:
Social Context 2010. Cancer Epidemiology Centre, Cancer Council Victoria.
Thursfield V, Farrugia H, Karahalios E, Giles G (2012). Cancer in Survival Victoria 2012: Estimates for Survival for 2006-2010 (and comparisons with earlier periods). Cancer Council Victoria, Melbourne.
Thursfield V, Farrugia H, Robertson P, Giles G (2010). Canstat: A digest of facts and figures on cancer. Cancer in Victoria 2008. Cancer Epidemiology Centre, Cancer Council Victoria.
Van Maele-Fabry G, Libotte V, Willems J, Lison D (2006). Review and meta-analysis of risk estimates for prostate cancer in pesticide manufacturing workers. Cancer Causes Control, 17, 353-73.
Van Wijngaarden E, Singer EA, Palapattu GS (2008). Prostate-specific antigen levels in relation to cadmium exposure and zinc intake: results from the 2001-2002 National Health and Nutrition Examination Survey. Prostate, 68, 122-8.
Verougstraete V, Lison D, Hotz P (2003). Cadmium, lung and prostate cancer: a systematic review of recent epidemiological data. J Toxicol Environ Health B Crit Rev, 6, 227-55.
Vinceti M, Venturelli M, Sighinolfi C (2007). Case-control study of toenail cadmium and prostate cancer risk in Italy. Science of the Total Environment, 373, 77-81.
Waalkes MP (2003). Cadmium carcinogenesis. Mutat Res, 533, 107-20.
White A, Coker AL, Du XL, Eggleston KS, Williams M (2011). Racial/ethnic disparities in survival among men diagnosed with prostate cancer in texas. Cancer, 117, 1080-8.
Wong O, Raabe GK (2000). A critical review of cancer epidemiology in the petroleum industry, with a meta-analysis of a combined database of more than 350,000 workers. Regulatory Toxicol & Pharmacol, 32, 78-98.
Xu X, Dailey AB, Talbott EO, et al (2010). Associations of serum concentrations of organochlorine pesticides with breast cancer and prostate cancer in U.S. adults. Environ Health Perspect, 118, 60-6.
Yang CY, Chang CC, Chiu HF (2008). Does arsenic exposure increase the risk for prostate cancer? J Toxicol Environ Health A, 71, 1559-63.
Young E, Kreiger N, Purdham J, Sass-Kortsak A (2009). Prostate cancer and driving occupations: could whole body vibration play a role? Int Archives of Occupational & Environmental Health, 82, 551-6.
Zeegers MPA, Friesema IHM, Goldbohm RA, Van Den Brandt PA (2004). A prospective study of occupation and prostate cancer risk. J Occupational and Environ Med, 46, 271-9.
