I
nte
rna
t
io
na
l J
o
urna
l o
f
P
u
bli
c
H
ea
lt
h Science
(
I
J
P
H
S)
Vo
l.
14
,
No
.
3
,
Sep
tem
b
er
20
25
,
p
p
.
1
1
0
9
~
1
118
I
SS
N:
2
2
5
2
-
8
8
0
6
,
DOI
: 1
0
.
1
1
5
9
1
/ijp
h
s
.
v
14
i
3
.
2
5
5
7
2
1109
J
o
ur
na
l ho
m
ep
a
g
e
:
h
ttp
:
//
ijp
h
s
.
ia
esco
r
e.
co
m
Rela
tions
hip
be
t
ween shi
ft
wo
rk a
nd t
he
risk of
colo
rect
a
l
ca
ncer amo
ng
M
o
ro
ccan
wo
men
H
a
m
za
E
lba
y
lek
,
So
um
ia
Am
m
o
r
La
b
o
r
a
t
o
r
y
o
f
P
h
a
r
ma
c
o
l
o
g
y
,
N
e
u
r
o
b
i
o
l
o
g
y
,
A
n
t
h
r
o
p
o
b
i
o
l
o
g
y
a
n
d
E
n
v
i
r
o
n
men
t
,
F
a
c
u
l
t
y
o
f
S
c
i
e
n
c
e
s
S
e
m
l
a
l
i
a
,
C
a
d
i
A
y
y
a
d
U
n
i
v
e
r
si
t
y
,
M
a
r
r
a
k
e
c
h
,
M
o
r
o
c
c
o
Art
icle
I
nfo
AB
S
T
RAC
T
A
r
ticle
his
to
r
y:
R
ec
eiv
ed
J
u
l
22
,
2
0
2
4
R
ev
is
ed
No
v
13
,
2
0
2
4
Acc
ep
ted
Dec
13
,
2
0
2
4
Co
lo
re
c
tal
c
a
n
c
e
r
(CRC)
is
a
p
u
b
li
c
h
e
a
lt
h
p
r
o
b
lem
wo
rl
d
wid
e
,
a
n
d
a
lso
in
M
o
ro
c
c
o
,
wit
h
7
.
9
%
o
f
n
e
w
c
a
n
c
e
r
c
a
se
s.
Die
tary
fa
c
to
rs
h
a
v
e
b
e
e
n
li
n
k
e
d
to
CRC
r
isk
;
h
o
we
v
e
r,
se
v
e
ra
l
m
o
d
ifi
a
b
le
risk
fa
c
to
rs
h
a
v
e
n
o
t
b
e
e
n
stu
d
ied
in
M
o
r
o
c
c
o
.
Th
is
stu
d
y
a
ime
d
to
e
x
p
lo
re
t
h
e
a
ss
o
c
iatio
n
b
e
twe
e
n
sh
ift
wo
rk
a
n
d
th
e
risk
o
f
c
o
lo
re
c
tal
c
a
n
c
e
r
a
m
o
n
g
M
o
r
o
c
c
a
n
wo
m
e
n
.
A
c
a
se
-
c
o
n
tro
l
stu
d
y
wa
s
c
o
n
d
u
c
ted
at
CHU
M
o
h
a
m
e
d
VI
M
a
rra
k
e
c
h
,
in
v
o
lv
i
n
g
1
6
5
c
a
se
s
a
n
d
1
6
5
c
o
n
tro
ls
.
Da
ta
we
r
e
c
o
ll
e
c
ted
u
sin
g
a
se
lf
-
a
d
m
in
istere
d
q
u
e
stio
n
n
a
ire.
F
o
r
g
e
n
e
ra
l
c
h
a
ra
c
teristics
,
we
u
se
d
t
h
e
Ch
i
-
s
q
u
a
re
tes
t
fo
r
c
a
teg
o
rica
l
v
a
ri
a
b
les
a
n
d
stu
d
e
n
t’
s
t
-
tes
t
o
r
M
a
n
n
-
W
h
it
n
e
y
U
fo
r
c
o
n
ti
n
u
o
u
s
v
a
riab
les
t
o
se
lec
t
c
o
n
f
o
u
n
d
i
n
g
fa
c
to
rs,
we
ra
n
lo
g
isti
c
re
g
re
ss
io
n
a
n
a
ly
sis
to
e
stim
a
te
o
d
d
s
ra
ti
o
s
a
n
d
9
5
%
c
o
n
fid
e
n
c
e
i
n
terv
a
ls.
F
i
n
d
i
n
g
s
fr
o
m
o
u
r
stu
d
y
sh
o
w
a
n
i
n
c
re
a
se
d
risk
o
f
CRC
fo
r
ro
tati
n
g
sh
ift
wo
rk
e
rs
OR
b
:1
.
7
4
(
9
5
%
CI:1
.
0
5
-
2
.
9
1
)
(
p
-
v
a
l
u
e
=
0
.
0
1
).
Wh
e
n
stra
ti
fied
b
y
t
u
m
o
r
lo
c
a
ti
o
n
,
n
ig
h
t
s
h
ift
wo
rk
wa
s
c
o
rre
late
d
with
a
n
in
c
r
e
a
se
d
risk
o
f
re
c
tal
c
a
n
c
e
r,
wh
i
le
stra
ti
fied
b
y
a
g
e
,
ro
tatin
g
sh
ift
wo
r
k
wa
s a
lso
c
o
rre
late
d
with
a
n
i
n
c
re
a
se
d
risk
o
f
CRC
a
m
o
n
g
th
o
se
a
g
e
d
4
5
to
6
5
y
e
a
rs
ORb
:
2
.
1
8
(9
5
%
CI:
1
.
0
3
-
4
.
7
9
)
(
p
-
v
a
lu
e
=
0
.
0
4
8
)
.
F
i
n
d
i
n
g
s
fr
o
m
th
is
st
u
d
y
may
b
e
h
e
lp
f
u
l
fo
r
fu
t
u
re
re
se
a
rc
h
in
M
o
ro
c
c
o
a
n
d
N
o
rth
Afric
a
n
c
o
u
n
tri
e
s
.
K
ey
w
o
r
d
s
:
C
ase
-
co
n
tr
o
l
C
o
lo
r
ec
tal
ca
n
ce
r
Mo
r
o
cc
o
Pre
v
en
tio
n
Sh
if
t w
o
r
k
T
h
is i
s
a
n
o
p
e
n
a
c
c
e
ss
a
rticle
u
n
d
e
r th
e
CC B
Y
-
SA
li
c
e
n
se
.
C
o
r
r
e
s
p
o
nd
ing
A
uth
o
r
:
Ham
za
E
lb
ay
lek
L
ab
o
r
ato
r
y
o
f
Ph
ar
m
ac
o
l
o
g
y
,
Neu
r
o
b
io
lo
g
y
,
A
n
th
r
o
p
o
b
io
l
o
g
y
an
d
E
n
v
i
r
o
n
m
e
n
t
Facu
lty
o
f
Scien
ce
s
Sem
lalia,
C
ad
i A
y
y
ad
Un
iv
er
s
ity
Ma
r
r
ak
ec
h
4
0
0
0
0
,
Mo
r
o
cc
o
E
m
ail:
h
am
za
.
elb
ay
lek
@
ce
d
.
u
ca
.
m
a
1.
I
NT
RO
D
UCT
I
O
N
C
o
lo
r
ec
tal
ca
n
ce
r
(
C
R
C
)
is
d
e
f
in
ed
as
a
ca
n
ce
r
th
at
af
f
ec
ts
eith
er
th
e
co
lo
n
o
r
r
ec
tu
m
.
B
ased
o
n
th
e
ca
n
ce
r
s
ite,
4
9
.
0
9
%
o
f
ca
s
es
ar
e
class
if
ied
as
co
lo
n
ca
n
ce
r
an
d
4
9
.
6
6
%
as
r
ec
tal
ca
n
ce
r
,
wh
ile
1
.
2
5
%
ar
e
class
if
ied
as
co
lo
r
ec
tal
ca
n
ce
r
s
[
1
]
.
C
R
C
is
k
n
o
wn
to
b
e
m
u
ltifa
cto
r
ial,
in
v
o
lv
in
g
b
o
th
en
v
ir
o
n
m
en
tal
an
d
g
en
etic
f
ac
to
r
s
[
2
]
.
Am
o
n
g
th
e
g
en
etic
f
ac
to
r
s
,
wh
ich
ar
e
n
o
n
-
m
o
d
if
iab
le,
ap
p
r
o
x
im
ately
2
0
%
o
f
C
R
C
ca
s
e
s
ar
e
lin
k
ed
to
2
g
e
n
etic
f
ac
to
r
s
:
f
am
ilial a
d
en
o
m
ato
u
s
p
o
ly
p
o
s
is
(
FA
P)
an
d
m
is
m
atch
r
ep
air
g
en
e
(
MM
R
)
.
Ag
e
is
an
o
th
er
n
o
n
-
m
o
d
if
ia
b
le
r
is
k
f
ac
to
r
f
o
r
C
R
C
,
with
a
lo
wer
in
cid
en
ce
an
d
m
o
r
tality
f
o
r
in
d
iv
id
u
als
u
n
d
er
4
5
y
ea
r
s
.
Ho
wev
er
,
r
ec
en
t
t
r
en
d
s
h
av
e
s
h
o
wn
an
in
cr
ea
s
in
g
in
cid
en
ce
o
f
C
R
C
am
o
n
g
y
o
u
n
g
er
p
o
p
u
latio
n
s
[
3
]
.
Sex
is
also
a
n
o
n
-
m
o
d
if
iab
le
r
is
k
f
ac
to
r
f
o
r
C
R
C
,
with
a
h
i
g
h
er
i
n
cid
en
ce
am
o
n
g
m
e
n
th
an
wo
m
en
[
4
]
.
On
th
e
o
th
er
h
an
d
,
n
u
m
e
r
o
u
s
m
o
d
if
iab
le
r
is
k
f
ac
to
r
s
h
av
e
b
ee
n
r
ec
o
g
n
ize
d
.
T
h
e
W
o
r
ld
C
an
ce
r
R
esear
ch
Fu
n
d
(
W
C
R
F)
h
as
estab
li
s
h
ed
s
tr
o
n
g
lin
k
s
b
etwe
en
th
ese
m
o
d
if
ia
b
le
r
is
k
f
ac
to
r
s
an
d
in
c
r
ea
s
e
d
o
r
d
ec
r
ea
s
e
d
r
is
k
o
f
C
R
C
.
Diet
h
as
b
ee
n
r
ec
o
g
n
ized
as
an
im
p
o
r
tan
t
m
o
d
if
i
ab
le
r
is
k
f
ac
t
o
r
f
o
r
C
R
C
,
s
u
ch
as,
e
x
ce
s
s
iv
e
co
n
s
u
m
p
tio
n
o
f
r
e
d
an
d
p
r
o
ce
s
s
ed
m
ea
ts
h
as
b
ee
n
s
h
o
wn
to
in
cr
ea
s
e
th
e
r
is
k
o
f
C
R
C
,
wh
ile
ce
r
ea
ls
co
n
tain
in
g
d
ietar
y
f
ib
e
r
o
f
f
e
r
a
p
r
o
tectiv
e
ef
f
ec
t
a
g
ain
s
t
C
R
C
.
L
i
k
ew
is
e
,
v
e
g
e
t
a
b
l
e
s
a
n
d
f
r
u
i
t
s
,
a
b
u
n
d
a
n
t
in
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8
8
0
6
I
n
t J Pu
b
lic
Hea
lth
Sci
,
Vo
l.
14
,
No
.
3
,
Sep
tem
b
er
20
25
:
1
1
0
9
-
1
1
1
8
1110
a
n
t
i
o
x
i
d
a
n
t
s
a
n
d
a
n
t
i
-
i
n
f
la
m
m
a
t
o
r
y
c
o
m
p
o
u
n
d
s
,
c
o
n
t
r
i
b
u
t
e
t
o
l
o
w
e
r
i
n
g
C
R
C
r
is
k
[
5
]
,
[
6
]
.
A
d
d
i
t
i
o
n
a
l
l
y
,
a
n
e
l
e
v
a
t
e
d
b
o
d
y
m
a
s
s
i
n
d
e
x
(
B
M
I
)
i
s
l
i
n
k
e
d
to
a
n
a
u
g
m
e
n
t
e
d
r
i
s
k
o
f
C
R
C
,
w
h
e
r
e
as
h
i
g
h
e
r
p
h
y
s
i
c
a
l
a
c
t
i
v
i
t
y
i
s
c
o
r
r
e
l
a
t
e
d
w
i
t
h
a
d
e
c
r
e
as
e
d
r
is
k
o
f
C
R
C
.
H
o
w
e
v
e
r
,
m
a
n
y
o
t
h
e
r
m
o
d
i
f
i
a
b
l
e
r
i
s
k
f
a
c
t
o
r
s
h
a
v
e
n
o
t
y
e
t
b
e
e
n
e
x
p
l
o
r
e
d
w
i
t
h
s
u
f
f
i
ci
e
n
t
s
u
p
p
o
r
t
i
n
g
e
v
i
d
e
n
c
e
[
7
]
.
I
n
r
ec
en
t
y
ea
r
s
,
C
R
C
h
as
b
ec
o
m
e
a
s
ig
n
if
ican
t
p
u
b
lic
h
ea
lt
h
p
r
o
b
lem
.
I
n
2
0
2
0
,
C
R
C
r
an
k
ed
th
ir
d
am
o
n
g
t
h
e
m
o
s
t
c
o
m
m
o
n
ca
n
ce
r
s
,
with
n
ea
r
l
y
2
m
illi
o
n
n
ew
ca
s
es
r
ep
o
r
te
d
wo
r
ld
w
id
e
f
o
r
b
o
th
s
ex
es
co
m
b
in
ed
.
I
n
ad
d
itio
n
,
C
R
C
is
th
e
s
ec
o
n
d
d
ea
d
lies
t
ca
n
ce
r
af
ter
b
r
ea
s
t
ca
n
ce
r
,
ca
u
s
in
g
9
3
5
,
1
7
3
(
9
.
4
%)
d
ea
th
s
,
with
an
in
cid
e
n
ce
r
at
e
o
f
2
3
.
4
an
d
1
6
.
2
p
er
1
0
0
,
0
0
0
f
o
r
m
en
an
d
wo
m
e
n
,
r
e
s
p
ec
tiv
ely
[
8
]
.
T
h
e
in
cid
en
ce
o
f
C
R
C
v
ar
ies
s
i
g
n
if
ican
tly
ac
r
o
s
s
d
if
f
er
en
t
g
eo
g
r
a
p
h
ic
r
e
g
io
n
s
,
d
e
v
elo
p
ed
o
r
h
ig
h
-
i
n
co
m
e
co
u
n
tr
ies
ten
d
t
o
h
av
e
a
h
ig
h
e
r
in
cid
en
ce
c
o
m
p
ar
e
d
to
d
ev
e
lo
p
in
g
o
r
m
id
d
le
-
an
d
lo
w
-
in
c
o
m
e
co
u
n
tr
ies
[
9
]
.
Ov
er
th
e
p
ast
d
ec
ad
e,
Mo
r
o
c
co
h
as
u
n
d
er
g
o
n
e
an
im
p
o
r
ta
n
t
in
d
u
s
tr
ial
tr
an
s
itio
n
,
lead
i
n
g
to
f
u
n
d
am
en
tal
ch
an
g
es
in
th
e
life
s
ty
le
o
f
its
p
o
p
u
latio
n
.
Ma
n
y
in
d
u
s
tr
ial
wo
r
k
er
s
ar
e
n
o
w
en
g
ag
ed
in
s
h
if
t
wo
r
k
,
in
clu
d
in
g
n
ig
h
t
s
h
if
t
an
d
r
o
tatin
g
s
h
if
ts
[
1
0
]
.
T
h
ese
life
s
ty
le
ch
an
g
es,
alo
n
g
with
d
ietar
y
f
ac
t
o
r
s
,
h
a
v
e
p
lay
ed
a
r
o
le
in
th
e
r
is
e
o
f
v
ar
io
u
s
d
is
ea
s
es
a
n
d
ca
n
ce
r
s
with
in
th
e
Mo
r
o
cc
an
p
o
p
u
latio
n
.
I
n
2
0
2
0
,
C
R
C
o
n
ce
ag
ain
r
an
k
e
d
th
ir
d
am
o
n
g
th
e
m
o
s
t
f
r
eq
u
en
tly
d
iag
n
o
s
ed
ca
n
ce
r
s
in
Mo
r
o
cc
o
,
r
e
p
r
esen
tin
g
7
.
5
%
o
f
all
ca
n
ce
r
ca
s
es,
with
an
in
cid
en
ce
o
f
1
1
.
3
p
er
1
0
0
,
0
0
0
f
o
r
b
o
th
s
ex
es
co
m
b
in
e
d
[
1
1
]
.
Un
f
o
r
tu
n
ately
,
Mo
r
o
c
co
lack
s
a
n
atio
n
al
ca
n
ce
r
r
e
g
is
tr
y
,
r
ely
i
n
g
in
s
te
ad
o
n
two
r
e
g
io
n
al
r
eg
is
tr
ies:
th
e
Gr
an
d
C
asab
lan
ca
r
e
g
io
n
,
w
h
er
e
C
R
C
r
ep
r
esen
ted
7
.
7
%
o
f
ca
s
es
b
etwe
en
2
0
1
3
a
n
d
2
0
1
7
,
with
an
in
cid
en
ce
o
f
9
p
er
100
,
0
0
0
f
o
r
b
o
t
h
s
ex
es
co
m
b
in
ed
.
Similar
ly
,
in
th
e
r
e
g
io
n
o
f
R
ab
at,
C
R
C
r
an
k
ed
th
ir
d
with
8
.
3
%
o
f
ca
n
ce
r
ca
s
es
f
o
r
m
e
n
an
d
7
.
8
%
f
o
r
wo
m
en
b
etwe
en
2
0
0
9
an
d
2
0
1
2
,
with
an
i
n
cid
en
ce
o
f
7
.
0
2
p
e
r
1
0
0
,
0
0
0
f
o
r
m
e
n
an
d
5
.
8
6
p
er
100
,
0
0
0
f
o
r
wo
m
en
[
1
2
]
,
[
1
3
]
.
T
h
e
I
n
ter
n
atio
n
al
Ag
en
cy
f
o
r
R
esear
ch
o
n
C
an
ce
r
(
I
AR
C
)
h
as
ca
teg
o
r
ized
s
h
if
t
wo
r
k
th
at
d
is
r
u
p
ts
th
e
cir
ca
d
ian
c
y
cle
as
a
“
p
r
o
b
ab
le
h
u
m
a
n
ca
r
cin
o
g
en
”
(
g
r
o
u
p
2
A)
[
1
4
]
.
So
m
e
ep
id
em
i
o
l
o
g
ical
s
tu
d
ies
h
av
e
alr
ea
d
y
estab
lis
h
ed
ev
id
en
ce
o
f
an
ass
o
ciatio
n
b
etwe
en
s
h
if
t
wo
r
k
an
d
b
r
ea
s
t
ca
n
ce
r
[
1
5
]
o
n
ly
a
f
ew
ep
id
em
io
lo
g
ical
s
tu
d
ies
in
h
i
g
h
-
in
co
m
e
co
u
n
tr
ies
h
av
e
ex
am
in
ed
th
e
ass
o
ciatio
n
b
etw
ee
n
s
h
if
t
wo
r
k
an
d
C
R
C
,
Pap
an
to
n
io
u
et
a
l
.
[
1
6
]
s
h
o
wed
a
n
in
c
r
ea
s
ed
r
is
k
o
f
C
R
C
o
n
s
h
if
t
wo
r
k
er
s
r
ep
o
r
t
in
g
an
OR
o
f
1
.
2
2
(
9
5
%
CI
: 1
.
0
4
-
1
.
4
3
)
.
Ho
wev
e
r
,
o
th
er
s
tu
d
ies h
av
e
s
u
g
g
ested
n
o
co
r
r
elatio
n
b
etwe
en
s
h
if
t w
o
r
k
an
d
C
R
C
r
is
k
,
s
u
ch
as
an
Au
s
tr
alian
ca
s
e
-
co
n
tr
o
l stu
d
y
wh
er
e
n
o
co
r
r
elatio
n
was f
o
u
n
d
b
etwe
en
s
h
if
t w
o
r
k
an
d
a
h
ig
h
er
r
is
k
o
f
C
R
C
wi
th
OR
:
0
.
9
5
(
9
5
%
CI
:
0
.
5
7
-
1
.
5
8
)
[
1
7
]
.
I
n
c
o
n
tr
a
s
t,
in
d
ev
elo
p
in
g
co
u
n
tr
ies
s
u
ch
as
Mo
r
o
cc
o
,
th
e
m
ajo
r
ity
o
f
t
h
e
s
tu
d
ies
m
ai
n
ly
f
o
c
u
s
o
n
d
iet,
p
h
y
s
ical
ac
tiv
ity
,
to
b
ac
co
an
d
alco
h
o
l
co
n
s
u
m
p
tio
n
,
lim
ited
d
ata
on
th
e
o
th
er
m
o
d
if
iab
le
r
is
k
f
ac
to
r
s
[
1
8
]
,
[
1
9
]
.
T
o
d
ate,
n
o
p
r
ev
io
u
s
s
tu
d
y
in
Mo
r
o
cc
o
h
as e
v
alu
ated
th
e
ef
f
ec
t
o
f
s
h
if
t
wo
r
k
o
n
C
R
C
r
is
k
.
T
h
e
p
o
ten
tial
ca
r
cin
o
g
en
ic
e
f
f
ec
t
o
f
cir
ca
d
ian
d
is
r
u
p
ti
o
n
s
ee
m
s
b
io
lo
g
ically
p
lau
s
ib
le,
s
in
ce
th
e
cir
ca
d
ian
cy
cle
co
n
tr
o
ls
s
ev
er
al
b
io
lo
g
ical
p
r
o
ce
s
s
es
an
d
m
ec
h
an
is
m
s
with
in
o
u
r
b
o
d
y
in
clu
d
in
g
its
ca
p
ac
ity
f
o
r
p
e
r
i
o
d
ic
tr
an
s
cr
ip
tio
n
,
an
d
t
h
e
r
eg
u
latio
n
o
f
d
eo
x
y
r
ib
o
n
u
cleic
a
cid
(
DNA
)
d
am
ag
e
an
d
r
ep
ai
r
[
2
0
]
.
T
h
e
s
tate
o
f
t
h
e
ar
t
f
o
r
th
is
r
e
s
ea
r
ch
h
ig
h
lig
h
ts
th
at
s
ev
er
al
r
is
k
f
ac
to
r
s
s
u
ch
as
d
iet,
B
MI
,
to
b
ac
co
,
an
d
alco
h
o
l
h
av
e
an
in
f
l
u
en
ce
o
n
C
R
C
r
is
k
,
s
u
p
p
o
r
ted
b
y
s
tr
o
n
g
ev
id
en
ce
.
Ho
wev
e
r
,
o
th
er
p
o
ten
tial
m
o
d
if
iab
le
r
is
k
f
ac
to
r
s
lik
e
s
h
i
f
t
wo
r
k
h
av
e
n
o
t
b
ee
n
f
u
lly
estab
li
s
h
ed
as
lin
k
ed
to
C
R
C
r
is
k
.
Nev
er
th
eless
,
all
th
e
s
tu
d
ies
in
v
esti
g
atin
g
th
e
lin
k
b
etwe
en
s
h
if
t
w
o
r
k
an
d
C
R
C
r
is
k
h
av
e
b
ee
n
c
o
n
d
u
cted
in
d
ev
elo
p
ed
co
u
n
tr
ies
with
in
co
n
clu
s
iv
e
a
n
d
co
n
f
lictin
g
r
esu
lts
th
at
s
til
l
to
n
ee
d
b
e
s
tu
d
ied
f
u
r
th
e
r
.
No
r
esear
ch
o
f
th
is
k
in
d
h
as
b
ee
n
co
n
d
u
cted
in
Mo
r
o
cc
o
.
T
o
b
u
ild
u
p
o
n
a
n
d
en
h
an
ce
p
r
ev
io
u
s
r
esear
ch
also
to
s
tr
en
g
th
e
n
an
d
g
u
id
e
f
u
tu
r
e
s
tu
d
ies,
t
h
e
ai
m
o
f
o
u
r
s
tu
d
y
was
to
e
x
am
in
e
t
h
e
p
o
ten
tial
r
elatio
n
s
h
i
p
b
etw
ee
n
s
h
if
t
wo
r
k
a
n
d
co
lo
r
ec
tal
ca
n
ce
r
r
is
k
,
wh
ile
a
cc
o
u
n
tin
g
f
o
r
all
p
o
s
s
ib
le
co
n
f
o
u
n
d
in
g
f
ac
t
o
r
s
o
f
C
R
C
f
o
r
d
if
f
er
en
t
p
r
o
f
ess
io
n
s
am
o
n
g
Mo
r
o
cc
an
wo
m
en
ac
co
r
d
in
g
t
o
tu
m
o
r
l
o
ca
tio
n
,
ag
e
ca
teg
o
r
ies,
an
d
d
u
r
atio
n
o
f
s
h
if
t
wo
r
k
in
Ma
r
r
ak
ec
h
,
Mo
r
o
cc
o
,
to
p
r
o
v
id
e
n
o
v
el
in
s
ig
h
ts
an
d
co
n
t
r
ib
u
te
to
b
o
th
lo
ca
l
an
d
g
lo
b
al
k
n
o
wled
g
e
o
n
th
e
s
u
b
ject.
2.
M
E
T
H
O
D
W
e
co
n
d
u
cted
a
ca
s
e
-
c
o
n
tr
o
l
s
tu
d
y
f
r
o
m
No
v
em
b
er
2
0
2
2
to
Feb
r
u
ar
y
2
0
2
4
at
t
h
e
Un
iv
er
s
ity
Ho
s
p
ital
C
en
ter
Mo
h
am
ed
VI
in
Ma
r
r
ak
ec
h
,
Mo
r
o
cc
o
.
T
h
e
p
ar
ticip
an
ts
o
f
th
e
s
tu
d
y
wer
e
r
ec
r
u
ited
ac
co
r
d
in
g
to
s
ev
er
al
elig
ib
ilit
y
cr
iter
ia.
F
o
r
ca
s
es,
ad
u
lt
wo
m
e
n
ag
ed
b
etwe
en
2
5
an
d
8
5
y
ea
r
s
wh
o
wer
e
p
r
o
f
ess
io
n
ally
ac
tiv
e
o
r
h
av
e
at
least
5
y
ea
r
s
o
f
p
r
o
f
ess
io
n
al
ex
p
er
ie
n
ce
,
with
a
co
n
f
ir
m
ed
h
is
to
p
ath
o
l
o
g
i
ca
l
C
R
C
d
iag
n
o
s
is
m
ad
e
with
in
th
e
p
ast
3
m
o
n
t
h
s
.
Ab
s
en
ce
o
f
c
o
g
n
itiv
e
o
r
ea
tin
g
d
is
o
r
d
er
s
,
wh
o
wer
e
a
d
m
itted
to
th
e
o
n
c
o
lo
g
y
an
d
h
em
ato
lo
g
y
ce
n
ter
d
u
r
i
n
g
th
e
r
ec
r
u
itm
e
n
t
p
e
r
io
d
in
th
e
o
r
d
er
o
f
ad
m
is
s
io
n
.
C
o
n
tr
o
ls
wer
e
r
ec
r
u
ited
f
r
o
m
th
e
s
am
e
h
o
s
p
ital
b
u
t
f
r
o
m
tr
au
m
ato
lo
g
y
d
ep
ar
tm
e
n
t,
co
n
tr
o
ls
wer
e
wo
m
en
ag
ed
b
etwe
e
n
2
5
an
d
8
5
y
ea
r
s
,
with
n
o
p
r
io
r
d
iag
n
o
s
is
o
f
an
y
ca
n
ce
r
o
r
g
astro
in
test
in
al
d
i
s
ea
s
e,
wh
o
wer
e
p
r
o
f
ess
io
n
ally
ac
tiv
e
o
r
h
a
d
at
least
5
y
ea
r
s
o
f
wo
r
k
ex
p
er
ie
n
ce
,
h
a
d
n
o
c
o
g
n
itiv
e
o
r
ea
tin
g
d
is
o
r
d
er
s
,
also
n
o
d
is
ea
s
e
r
eq
u
ir
in
g
a
s
p
ec
if
ic
d
iet,
an
d
n
o
f
am
ily
h
is
to
r
y
o
f
C
R
C
ca
s
es
in
f
ir
s
t
-
d
eg
r
ee
r
elativ
es,
wh
o
atten
d
ed
th
e
h
o
s
p
ital
d
u
r
in
g
th
e
s
am
e
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t J Pu
b
lic
Hea
lth
Sci
I
SS
N:
2252
-
8
8
0
6
R
ela
tio
n
s
h
ip
b
etw
ee
n
s
h
ift w
o
r
k
a
n
d
th
e
r
is
k
o
f c
o
lo
r
ec
ta
l c
a
n
ce
r
a
mo
n
g
M
o
r
o
cc
a
n
…
(
Ha
mza
E
lb
a
ylek
)
1111
p
er
io
d
as
ca
s
es.
C
ases
an
d
c
o
n
tr
o
ls
wer
e
m
atch
ed
ac
c
o
r
d
in
g
to
ag
e
(
±
3
y
ea
r
s
)
f
o
r
ca
s
es
was
th
e
ag
e
at
d
iag
n
o
s
is
an
d
co
n
tr
o
ls
a
g
e
at
th
e
i
n
ter
v
iew,
with
a
r
atio
o
f
1
ca
s
e
t
o
1
c
o
n
tr
o
l.
Prio
r
to
t
h
e
r
ec
r
u
itm
en
t
p
r
o
ce
s
s
,
th
e
s
am
p
le
s
ize
was
ca
lcu
lated
u
s
in
g
th
e
a
p
p
r
o
p
r
ia
te
ca
s
e
-
co
n
tr
o
l
s
tu
d
y
f
o
r
m
u
la
[
2
1
]
,
th
e
m
in
im
u
m
r
eq
u
ir
ed
s
am
p
le
s
ize
was
1
5
0
ca
s
es
an
d
1
5
0
co
n
tr
o
ls
,
to
d
etec
t
an
o
d
d
s
r
atio
(
OR
)
o
f
2
f
o
r
2
5
%
o
f
ex
p
o
s
ed
co
n
tr
o
ls
,
with
a
p
o
wer
o
f
8
0
%
an
d
5
%
ty
p
e
I
e
r
r
o
r
.
T
h
e
s
tu
d
y
p
r
o
to
co
l
was
ap
p
r
o
v
ed
b
y
r
esear
ch
eth
ics
co
m
m
ittee
o
f
th
e
M
o
r
o
cc
a
n
as
s
o
ciatio
n
f
o
r
r
esear
ch
an
d
eth
i
cs
u
n
d
er
th
e
id
en
tifie
r
1
2
-
R
E
C
-
2
0
2
2
.
A
p
ilo
t
test
o
f
th
e
q
u
esti
o
n
n
air
e
was
co
n
d
u
cted
o
n
a
s
am
p
le
o
f
3
0
p
a
r
ticip
an
ts
b
ef
o
r
e
th
e
s
tu
d
y
to
ev
alu
ate
an
d
m
ak
e
ap
p
r
o
p
r
iate
m
o
d
if
icatio
n
s
to
t
h
e
q
u
esti
o
n
n
ai
r
e.
E
ac
h
p
ar
ticip
an
t w
as f
ir
s
t a
p
p
r
o
ac
h
ed
to
ev
alu
ate
th
eir
elig
ib
ilit
y
.
T
h
e
in
v
esti
g
ato
r
ex
p
lain
ed
th
e
aim
an
d
p
u
r
p
o
s
e
o
f
th
e
s
tu
d
y
to
ea
ch
p
ar
ticip
an
t.
W
h
en
th
e
in
v
esti
g
ato
r
o
b
tain
ed
th
e
w
r
itten
an
d
in
f
o
r
m
ed
co
n
s
en
t
o
f
th
e
p
ar
ticip
an
t,
we
p
r
o
ce
ed
ed
to
a
f
ac
e
-
to
-
f
ac
e
i
n
ter
v
iew
o
f
an
av
er
a
g
e
d
u
r
atio
n
o
f
2
5
m
in
u
tes
.
Data
wer
e
co
llected
u
s
in
g
a
q
u
esti
o
n
n
air
e
d
iv
id
ed
in
to
3
s
ec
tio
n
s
.
T
h
e
f
ir
s
t
s
ec
tio
n
co
n
ce
r
n
ed
th
e
g
e
n
er
al
ch
ar
ac
ter
is
tics
o
f
th
e
p
ar
ticip
an
ts
: a
g
e
as a
co
n
tin
u
o
u
s
v
ar
iab
le,
weig
h
t a
s
a
co
n
tin
u
o
u
s
v
ar
i
ab
le
,
f
o
r
ca
s
es
,
th
e
weig
h
t
r
ec
o
r
d
ed
p
r
i
o
r
t
o
C
R
C
s
y
m
p
to
m
s
,
wh
ile
f
o
r
co
n
tr
o
ls
,
weig
h
t
was
m
ea
s
u
r
ed
o
n
th
e
d
a
y
o
f
t
h
e
in
ter
v
iew,
r
ec
o
r
d
e
d
to
th
e
n
ea
r
est
1
0
0
g
u
s
in
g
an
elec
tr
o
n
ic
Seca
8
0
3
s
ca
le.
Heig
h
t
was
tr
ea
ted
a
s
a
co
n
tin
u
o
u
s
v
ar
iab
le
an
d
was
m
ea
s
u
r
ed
d
u
r
in
g
th
e
in
ter
v
i
ew
to
th
e
n
ea
r
est
0
.
1
cm
u
s
in
g
a
C
o
m
ed
tap
e
m
ea
s
u
r
e.
B
MI
was
ca
lcu
lated
u
s
in
g
th
e
ap
p
r
o
p
r
iate
f
o
r
m
u
la
b
ased
o
n
h
eig
h
t
an
d
weig
h
t
(
k
g
/m
2
)
ca
teg
o
r
ized
in
to
4
g
r
o
u
p
s
in
lin
e
with
th
e
W
HO
cla
s
s
if
icat
io
n
[
2
2
]
u
n
d
e
r
weig
h
t
f
o
r
an
B
MI
<1
8
.
5
,
n
o
r
m
al
B
MI
b
etwe
en
1
8
.
5
-
2
4
.
9
,
o
v
er
weig
h
t
B
MI
:
2
5
-
29.
9
,
an
d
f
in
ally
o
b
esit
y
f
o
r
an
B
MI
≥
3
0
.
E
d
u
ca
tio
n
al
lev
el
was
d
iv
id
ed
in
to
4
ca
teg
o
r
ical
v
ar
ia
b
les:
illi
ter
ate,
p
r
im
ar
y
,
s
ec
o
n
d
ar
y
,
an
d
u
n
iv
er
s
ity
.
R
esid
en
cy
was
ca
teg
o
r
ized
as
u
r
b
an
o
r
r
u
r
al.
Ph
y
s
ical
ac
tiv
ity
was
a
s
s
es
s
ed
b
ased
o
n
th
e
g
lo
b
al
p
h
y
s
ical
ac
tiv
ity
q
u
esti
o
n
n
air
e
(
GPAQ)
[
2
3
]
,
an
d
class
if
ied
in
to
th
r
ee
g
r
o
u
p
s
:
l
o
w
<6
0
0
ME
T
-
m
in
/wee
k
,
m
o
d
er
ate
6
0
0
–
3
,
0
0
0
ME
T
-
m
in
/wee
k
,
an
d
h
ig
h
≥3
,
0
0
0
ME
T
-
m
in
/wee
k
,
f
am
il
y
h
is
to
r
y
o
f
co
lo
r
ec
tal
ca
n
ce
r
was
r
ec
o
r
d
ed
as
eith
er
‘
y
es
’
o
r
‘
no
’
.
T
h
e
s
ec
o
n
d
s
ec
tio
n
o
f
th
e
q
u
esti
o
n
n
ai
r
e
was
a
v
alid
ated
s
em
i
q
u
an
tita
tiv
e
f
o
o
d
f
r
eq
u
en
cy
q
u
esti
o
n
n
air
e
(
SQ
-
FF
Q)
f
o
r
M
o
r
o
cc
a
n
a
d
u
lt
p
o
p
u
latio
n
[
2
4
]
.
Usi
n
g
th
e
Mo
r
o
cc
an
ta
b
le
o
f
f
o
o
d
co
m
p
o
s
itio
n
[
2
5
]
,
W
e
esti
m
ated
th
e
d
aily
q
u
an
tity
o
f
f
o
o
d
co
n
s
u
m
ed
b
y
ea
ch
p
a
r
ticip
an
t
b
y
m
u
ltip
l
y
in
g
th
e
f
r
eq
u
e
n
cy
o
f
co
n
s
u
m
p
tio
n
b
y
th
e
p
o
r
tio
n
s
izes.
W
e
al
s
o
co
n
v
er
ted
th
e
co
n
s
u
m
ed
f
o
o
d
s
in
to
n
u
tr
ien
t
in
tak
es
b
y
m
u
ltip
ly
in
g
th
e
q
u
an
tity
o
f
ea
c
h
f
o
o
d
b
y
its
n
u
tr
ien
t
co
n
ten
t
(
p
er
1
0
0
g
)
.
T
o
ca
lcu
late
e
n
er
g
y
in
t
ak
e,
we
m
u
ltip
lied
th
e
d
aily
i
n
tak
e
o
f
ea
c
h
f
o
o
d
item
b
y
its
ca
lo
r
ic
co
n
ten
t.
T
h
e
th
ir
d
s
ec
tio
n
o
f
th
e
q
u
esti
o
n
n
air
e
was
to
ass
ess
s
h
if
t
wo
r
k
r
etr
o
s
p
ec
tiv
ely
f
o
r
ev
er
y
jo
b
h
eld
f
o
r
a
m
i
n
im
u
m
o
f
o
n
e
y
ea
r
,
in
clu
d
i
n
g
d
eta
ils
o
n
th
e
ty
p
e
o
f
s
h
if
t,
d
u
r
ati
o
n
,
an
d
n
u
m
b
e
r
o
f
h
o
u
r
s
wo
r
k
ed
.
T
h
e
in
v
esti
g
ato
r
s
d
ef
in
ed
3
ca
teg
o
r
ies
o
f
s
h
if
t
wo
r
k
b
ased
o
n
t
h
e
co
m
m
o
n
s
h
if
t
s
ch
ed
u
les
in
Mo
r
o
cc
an
f
ac
to
r
ies:
d
ay
s
h
if
t
wo
r
k
,
n
i
g
h
t sh
if
t w
o
r
k
,
an
d
r
o
t
atin
g
s
h
if
t w
o
r
k
:
-
Day
s
h
if
t
wo
r
k
was
d
eter
m
i
n
ed
as
wo
r
k
in
g
≥
4
h
o
u
r
s
b
etw
ee
n
6
:0
0
an
d
2
0
:0
0
f
o
r
at
lea
s
t
1
5
d
ay
s
p
er
m
o
n
th
;
-
Nig
h
t
s
h
if
t
wo
r
k
was
d
eter
m
in
ed
as
wo
r
k
in
g
≥
4
h
o
u
r
s
b
e
twee
n
2
2
:0
0
an
d
5
:0
0
f
o
r
at
least
1
5
d
ay
s
a
m
o
n
th
;
-
F
in
ally
,
r
o
tatin
g
wo
r
k
r
e
f
er
r
ed
to
an
y
s
h
if
t t
h
at
alter
n
ates b
et
wee
n
th
e
two
s
h
if
ts
o
f
d
a
y
an
d
n
ig
h
t.
Fo
r
ea
ch
p
ar
ticip
a
n
t,
we
ass
es
s
ed
:
Sh
if
t
o
f
wo
r
k
: d
ay
s
h
if
t
w
o
r
k
,
r
o
tatin
g
s
h
if
t
wo
r
k
,
n
i
g
h
t sh
if
t
wo
r
k
,
an
d
th
e
d
u
r
atio
n
o
f
ea
ch
wo
r
k
h
el
d
.
C
u
m
u
lativ
e
y
ea
r
s
o
f
r
o
tatin
g
a
n
d
n
ig
h
t
s
h
if
t
w
o
r
k
wer
e
ca
teg
o
r
ized
in
t
o
q
u
ar
tiles
b
ased
o
n
th
e
d
is
tr
ib
u
tio
n
am
o
n
g
co
n
tr
o
ls
.
Fo
r
r
o
tatin
g
s
h
if
t
wo
r
k
th
e
q
u
ar
tiles
wer
e:
Q1
(
<8
)
Q2
(
≤
8
-
1
3
<)
,
Q3
(
≤
1
3
-
1
7
<)
,
a
n
d
Q4
(
≥
1
7
)
.
W
h
ile
f
o
r
c
u
m
u
lativ
e
y
ea
r
s
o
f
n
i
g
h
t
s
h
if
t
w
o
r
k
th
e
q
u
ar
ti
les
wer
e:
Q1
(
<2
)
,
Q2
(
≤
2
-
5
<)
,
Q3
(
≤
5
-
8
<)
,
a
n
d
Q4
(
≥
8
)
.
T
h
e
g
en
er
al
ch
a
r
ac
ter
is
tics
o
f
th
e
p
o
p
u
latio
n
in
clu
d
e
d
ca
teg
o
r
ical
v
ar
iab
les
illu
s
tr
ated
as
f
r
eq
u
en
cies
an
d
co
n
tin
u
o
u
s
v
a
r
iab
les
illu
s
tr
ated
as
m
ea
n
s
(
±
SD)
.
W
e
p
er
f
o
r
m
ed
a
b
iv
ar
iate
a
n
aly
s
is
to
ass
es
s
th
e
d
if
f
er
en
ce
s
b
etwe
en
ca
s
es
a
n
d
co
n
t
r
o
ls
,
f
o
r
ca
te
g
o
r
ical
v
ar
iab
les,
we
u
s
ed
th
e
C
h
i
-
s
q
u
ar
e
test
,
an
d
f
o
r
co
n
tin
u
o
u
s
v
ar
iab
les
,
we
u
s
ed
Stu
d
en
t’
s
t
-
test
o
r
Ma
n
n
-
W
h
itn
ey
U
(
d
ep
en
d
in
g
o
n
t
h
e
n
o
r
m
ality
o
f
th
e
d
is
tr
ib
u
tio
n
)
.
T
o
ex
am
in
e
th
e
co
r
r
elatio
n
b
etwe
en
s
h
if
t
wo
r
k
an
d
C
R
C
r
is
k
,
we
p
er
f
o
r
m
e
d
lo
g
is
tic
r
e
g
r
ess
io
n
an
aly
s
is
to
esti
m
ate
O
d
d
s
R
at
io
s
an
d
9
5
%
co
n
f
i
d
en
ce
in
ter
v
als
(
C
I
)
.
T
wo
m
o
d
els
wer
e
c
o
n
s
id
er
ed
:
th
e
f
ir
s
t
cr
u
d
e
m
o
d
el
(
OR
a)
ad
ju
s
ted
o
n
ly
f
o
r
ag
e
(
±
3
y
ea
r
s
)
,
an
d
a
s
ec
o
n
d
m
o
d
el
ad
ju
s
ted
f
o
r
co
n
f
o
u
n
d
in
g
f
ac
to
r
s
b
ased
o
n
th
e
g
en
er
al
c
h
ar
ac
ter
is
tics
o
f
th
e
p
o
p
u
latio
n
(
OR
b
)
ad
ju
s
ted
f
o
r
:
ed
u
ca
tio
n
al
lev
el
(
illi
ter
ate,
p
r
im
ar
y
,
s
ec
o
n
d
ar
y
,
u
n
iv
er
s
i
ty
)
;
m
ar
ital
s
tatu
s
(
n
ev
er
m
ar
r
ied
,
m
a
r
r
ied
,
d
iv
o
r
ce
d
,
w
id
o
wed
)
;
r
esid
en
c
y
(
u
r
b
an
,
r
u
r
al)
;
B
MI
(
u
n
d
er
wei
g
h
t,
n
o
r
m
al,
o
v
er
weig
h
t,
o
b
esi
ty
)
;
p
h
y
s
ical
ac
tiv
ity
(
lo
w,
m
o
d
er
ate,
h
ig
h
)
;
to
tal
en
er
g
y
i
n
tak
e
(
k
ca
l
)
as
co
n
ti
n
u
o
u
s
v
a
r
iab
le;
f
ib
er
I
n
tak
e
(
g
/d
ay
)
as
co
n
tin
u
o
u
s
v
ar
iab
le;
ca
lciu
m
I
n
tak
e
(
m
g
/d
ay
)
as
co
n
tin
u
o
u
s
v
ar
ia
b
le;
r
ed
m
ea
t
in
tak
e
(
g
/wee
k
)
as
co
n
tin
u
o
u
s
v
ar
ia
b
le.
All
g
r
o
u
p
s
o
f
s
h
if
t
wo
r
k
an
d
cu
m
u
lativ
e
y
ea
r
s
o
f
s
h
if
t
wo
r
k
wer
e
c
o
m
p
a
r
ed
to
d
ay
s
h
if
t
wo
r
k
e
r
s
,
wh
o
s
er
v
ed
as
t
h
e
r
ef
er
e
n
ce
g
r
o
u
p
,
th
e
s
ig
n
if
ican
ce
lev
el
was
est
ab
lis
h
ed
at
p
-
v
alu
e
<0
.
0
5
.
Pa
r
ticip
an
ts
with
m
is
s
in
g
d
ata
wer
e
ex
clu
d
ed
f
r
o
m
th
e
s
tu
d
y
p
r
i
o
r
to
t
h
e
s
tatis
tica
l a
n
aly
s
is
.
we
u
s
ed
SP
SS
v
2
3
s
o
f
twar
e
to
en
ter
a
n
d
an
al
y
ze
d
ata.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8
8
0
6
I
n
t J Pu
b
lic
Hea
lth
Sci
,
Vo
l.
14
,
No
.
3
,
Sep
tem
b
er
20
25
:
1
1
0
9
-
1
1
1
8
1112
3.
RE
SU
L
T
S AN
D
D
I
SCU
SS
I
O
N
3
.
1
.
G
ener
a
l
cha
ra
ct
er
is
t
ics
o
f
t
he
pa
rt
icipa
nts
O
u
r
s
t
u
d
y
i
n
c
l
u
d
e
d
3
3
0
p
a
r
t
i
c
i
p
a
n
t
s
,
d
i
v
i
d
e
d
i
n
t
o
1
6
5
c
a
s
e
s
a
n
d
1
6
5
c
o
n
t
r
o
l
s
.
O
u
r
i
n
v
e
s
t
i
g
at
o
r
s
a
p
p
r
o
a
c
h
e
d
1
7
4
e
l
i
g
i
b
l
e
c
a
s
e
s
,
1
6
8
o
f
w
h
o
m
a
c
c
e
p
t
e
d
t
o
p
a
r
t
i
c
i
p
a
te
,
w
i
t
h
9
6
.
5
5
%
o
f
p
a
r
t
i
ci
p
a
t
i
o
n
r
a
t
e
.
T
h
r
e
e
c
a
s
es
w
e
r
e
e
x
c
l
u
d
e
d
b
e
f
o
r
e
s
ta
t
i
s
t
i
c
al
a
n
a
l
y
s
is
d
u
e
t
o
i
n
c
o
m
p
l
e
t
e
o
r
i
n
v
a
li
d
a
t
e
d
d
a
ta
.
A
t
o
t
a
l
o
f
1
8
0
e
l
i
g
i
b
l
e
c
o
n
t
r
o
l
s
we
r
e
a
p
p
r
o
a
c
h
e
d
1
7
0
o
f
t
h
e
m
a
c
c
e
p
te
d
t
o
p
a
r
t
ic
i
p
a
t
e
(
9
4
.
4
4
%
)
,
2
c
o
n
t
r
o
ls
w
e
r
e
e
x
c
l
u
d
e
d
f
r
o
m
t
h
e
s
t
u
d
y
f
o
r
i
n
c
o
m
p
l
e
t
e
o
r
i
n
v
a
l
i
d
a
t
e
d
d
a
t
a
a
n
d
3
a
d
d
i
t
i
o
n
a
l
w
e
r
e
e
x
c
l
u
d
e
d
t
o
m
a
t
c
h
c
a
s
e
p
a
r
t
ic
i
p
a
n
t
s
a
c
c
o
r
d
i
n
g
t
o
m
a
t
c
h
i
n
g
p
a
r
a
m
e
t
e
r
s
.
T
h
e
m
ea
n
a
g
e
o
f
c
a
s
e
s
w
as
4
9
±
6
.
1
3
y
e
a
r
s
a
n
d
5
0
±
4
.
2
5
y
e
a
r
s
f
o
r
c
o
n
t
r
o
l
s
(
p
-
v
a
l
u
e
=
0
.
8
6
)
,
r
e
g
a
r
d
i
n
g
e
d
u
c
a
t
i
o
n
a
l
l
ev
e
l
n
e
a
r
l
y
t
h
e
h
a
l
f
o
f
c
as
e
s
(
4
7
.
2
7
%
)
w
e
r
e
i
l
li
t
e
r
at
e
,
c
o
m
p
a
r
ed
t
o
o
n
l
y
3
1
.
5
1
%
o
f
c
o
n
t
r
o
l
s
.
F
o
r
m
a
r
i
ta
l
s
t
at
u
s
,
2
6
.
0
6
%
o
f
c
a
s
e
s
h
a
d
n
e
v
e
r
b
ee
n
m
a
r
r
i
e
d
v
e
r
s
u
s
1
6
.
3
6
%
f
o
r
c
o
n
t
r
o
l
s
,
m
a
r
r
i
e
d
w
o
m
e
n
r
e
p
r
e
s
e
n
t
e
d
5
2
.
1
2
%
o
f
c
a
s
e
s
a
n
d
7
1
.
5
1
%
o
f
c
o
n
t
r
o
ls
,
r
e
s
u
lt
i
n
g
i
n
a
s
i
g
n
i
f
i
c
a
n
t
d
i
f
f
e
r
e
n
c
e
(
p
-
v
a
l
u
e
=
0
.
0
0
2
)
f
o
r
m
a
r
i
t
a
l
s
t
a
t
u
s
.
T
h
e
m
a
j
o
r
i
t
y
o
f
c
o
n
t
r
o
l
s
l
i
v
e
d
i
n
u
r
b
a
n
a
r
e
a
s
(
8
6
.
6
6
%
)
a
g
a
i
n
s
t
5
3
.
3
3
%
o
f
c
a
s
e
s
,
s
h
o
w
i
n
g
a
s
i
g
n
i
f
i
c
a
n
t
d
i
f
f
e
r
e
n
c
e
(
p
-
v
a
l
u
e
<
0
.
0
0
1
)
.
M
o
r
e
t
h
a
n
h
a
l
f
o
f
c
o
n
t
r
o
l
s
(
6
3
.
0
3
%
)
h
a
d
a
n
o
r
m
a
l
B
M
I
,
w
h
i
l
e
h
a
l
f
o
f
t
h
e
c
a
s
e
s
(
5
0
.
2
9
%
)
w
e
r
e
a
b
o
v
e
t
h
e
n
o
r
m
a
l
r
a
n
g
e
(
o
v
e
r
w
e
i
g
h
t
a
n
d
o
b
e
s
e
)
(
p
-
v
a
l
u
e
<
0
.
0
0
1
)
.
A
d
d
i
t
i
o
n
a
l
l
y
,
7
5
.
1
5
%
o
f
c
a
s
e
s
h
a
d
l
o
w
p
h
y
s
i
c
a
l
a
c
t
i
v
i
t
y
,
c
o
m
p
a
r
e
d
t
o
5
1
.
8
2
%
o
f
c
o
n
t
r
o
l
s
,
a
l
s
o
o
n
l
y
2
2
.
4
2
%
o
f
c
a
s
e
s
h
a
d
m
o
d
e
r
a
t
e
p
h
y
s
i
c
a
l
a
c
t
i
v
i
t
y
v
e
r
s
u
s
3
7
.
5
7
%
o
f
c
o
n
t
r
o
l
s
(
p
-
v
a
l
u
e
<
0
.
0
0
1
)
.
N
o
s
i
g
n
i
f
i
c
a
n
t
d
i
f
f
e
r
e
n
c
e
(
p
-
v
a
l
u
e
=
0
.
2
5
1
)
w
a
s
o
b
s
e
r
v
e
d
c
o
n
c
e
r
n
i
n
g
f
a
m
i
l
y
h
i
s
t
o
r
y
o
f
C
R
C
.
T
h
e
t
o
t
a
l
e
n
e
r
g
y
i
n
t
a
k
e
c
o
n
s
u
m
e
d
b
y
c
a
s
e
s
w
a
s
h
i
g
h
e
r
t
h
a
n
c
o
n
t
r
o
l
s
,
w
i
t
h
a
s
i
g
n
i
f
i
c
a
n
t
d
i
f
f
e
r
e
n
c
e
(
p
-
v
a
l
u
e
<
0
.
0
0
1
)
.
I
n
c
o
n
t
r
a
s
t
,
f
i
b
e
r
i
n
t
a
k
e
w
a
s
h
i
g
h
e
r
a
m
o
n
g
c
o
n
t
r
o
l
s
t
h
a
n
c
a
s
e
s
(
p
-
v
a
l
u
e
<
0
.
0
0
1
)
a
s
s
h
o
w
n
i
n
T
a
b
l
e
1
.
O
u
r
f
i
n
d
i
n
g
s
a
r
e
c
o
n
s
i
s
t
e
n
t
w
i
t
h
a
n
o
t
h
e
r
M
o
r
o
c
c
a
n
c
a
s
e
-
c
o
n
t
r
o
l
s
t
u
d
y
c
o
n
d
u
c
t
e
d
b
y
K
i
n
a
n
y
e
t
a
l
.
[
2
6
]
w
h
i
c
h
r
e
p
o
r
t
e
d
t
h
a
t
o
v
e
r
5
0
%
o
f
b
o
t
h
c
a
s
e
s
a
n
d
c
o
n
t
r
o
l
s
w
e
r
e
m
a
r
r
i
e
d
,
a
n
d
o
v
e
r
3
0
%
o
f
c
a
s
e
s
l
i
v
e
d
i
n
r
u
r
a
l
a
r
e
a
s
,
s
i
m
i
l
a
r
l
y
t
o
o
u
r
s
t
u
d
y
n
e
a
r
l
y
t
h
e
h
a
l
f
o
f
c
a
s
e
s
w
e
r
e
i
l
l
e
t
e
r
a
t
e
a
n
d
o
n
l
y
3
8
%
o
f
c
a
s
e
s
h
a
d
n
o
r
m
a
l
B
M
I
.
H
o
w
e
v
e
r
,
i
n
c
o
n
t
r
a
s
t
w
i
t
h
o
u
r
s
t
u
d
y
,
D
e
o
u
l
a
e
t
a
l
.
[
2
7
]
r
e
p
o
r
t
e
d
t
h
a
t
m
o
r
e
t
h
a
n
8
0
%
o
f
c
a
s
e
s
w
e
r
e
i
l
l
i
t
e
r
a
t
e
,
o
n
l
y
1
.
2
%
o
f
c
a
s
e
s
h
a
d
a
n
o
r
m
a
l
B
M
I
,
a
n
d
o
v
e
r
8
0
%
w
e
r
e
m
a
r
r
i
e
d
.
T
ab
le
1
.
Ov
e
r
v
iew
o
f
p
ar
ticip
an
t g
en
er
al
c
h
ar
ac
ter
is
tics
in
a
Mo
r
o
cc
an
w
o
m
en
ca
s
e
co
n
tr
o
l stu
d
y
C
h
a
r
a
c
t
e
r
i
s
t
i
c
s
C
a
ses
(
%)
C
o
n
t
r
o
l
s
(
%)
p
-
v
a
l
u
e
#
E
d
u
c
a
t
i
o
n
a
l
l
e
v
e
l
0
.
0
0
2
I
l
l
i
t
e
r
a
t
e
7
8
(
4
7
.
2
7
)
5
2
(
3
1
.
5
1
)
P
r
i
mary
4
7
(
2
8
.
4
8
)
3
9
(
2
3
.
6
3
)
S
e
c
o
n
d
a
r
y
3
5
(
2
1
.
2
1
)
6
1
(
3
6
.
9
6
)
U
n
i
v
e
r
si
t
y
5
(
3
.
0
4
)
1
3
(
7
.
8
7
)
#
M
a
r
i
t
a
l
s
t
a
t
u
s
0
.
0
0
2
N
e
v
e
r
marr
i
e
d
4
3
(
2
6
.
0
6
)
2
7
(
1
6
.
3
6
)
M
a
r
r
i
e
d
8
6
(
5
2
.
1
2
)
1
1
8
(
7
1
.
5
1
)
D
i
v
o
r
c
e
d
1
1
(
6
.
6
6
)
3
(
1
.
8
1
)
W
i
d
o
w
e
d
2
5
(
1
5
.
1
5
)
1
7
(
1
0
.
3
0
)
#
R
e
si
d
e
n
c
y
<
0
.
0
0
1
U
r
b
a
n
8
8
(
5
3
.
3
3
)
1
4
3
(
8
6
.
6
6
)
R
u
r
a
l
7
7
(
4
6
.
6
7
)
2
2
(
1
3
.
3
4
)
#
B
M
I
<
0
.
0
0
1
U
n
d
e
r
w
e
i
g
h
t
1
5
(
9
.
0
9
)
2
4
(
1
4
.
5
4
)
N
o
r
mal
6
7
(
4
0
.
6
0
)
1
0
4
(
6
3
.
0
3
)
O
v
e
r
w
e
i
g
h
t
6
5
(
3
9
.
3
9
)
2
1
(
1
2
.
7
2
)
O
b
e
si
t
y
1
8
(
1
0
.
9
0
)
1
6
(
9
.
6
9
)
#
P
h
y
s
i
c
a
l
a
c
t
i
v
i
t
y
<
0
.
0
0
1
Lo
w
1
2
4
(
7
5
.
1
5
)
8
5
(
5
1
.
8
2
)
M
o
d
e
r
a
t
e
3
7
(
2
2
.
4
2
)
6
2
(
3
7
.
5
7
)
H
i
g
h
4
(
2
.
4
2
)
1
8
(
1
0
.
9
0
)
#
F
a
m
i
l
y
h
i
st
o
r
y
o
f
C
R
C
0
.
2
5
1
No
1
6
0
(
9
6
.
9
6
)
1
6
3
(
9
8
.
7
8
)
Y
e
s
5
(
3
.
0
4
)
2
(
1
.
2
2
)
C
a
ses
m
e
a
n
±
S
D
C
o
n
t
r
o
l
m
e
a
n
±
S
D
#
A
g
e
4
9
±
6
.
1
3
5
0
±
4
.
2
5
0
.
8
6
To
t
a
l
e
n
e
r
g
y
i
n
t
a
k
e
(
K
c
a
l
/
d
a
y
)
2
4
7
9
.
3
1
±
8
4
.
1
3
2
1
3
0
.
1
5
±
2
0
.
9
2
<
0
.
0
0
1
F
i
b
e
r
i
n
t
a
k
e
(
g
/
d
a
y
)
1
8
.
0
4
±
3
.
2
1
2
4
.
1
3
±
2
.
6
4
<
0
.
0
0
1
C
a
l
c
i
u
m
i
n
t
a
k
e
(
mg
/
d
a
y
)
7
6
4
.
1
2
±
4
.
2
2
7
5
8
.
8
1
±
3
.
4
0
<
0
.
0
0
1
F
o
l
a
t
e
i
n
t
a
k
e
(
mc
g
/
d
a
y
)
1
2
0
.
1
4
±
1
0
.
2
6
1
2
2
.
0
3
±
9
.
1
8
0
.
0
7
8
V
i
t
a
m
i
n
D
i
n
t
a
k
e
(
m
c
g
/
d
a
y
)
1
.
8
±
1
.
0
2
1
.
9
±
1
.
0
7
0
.
3
8
5
R
e
d
me
a
t
i
n
t
a
k
e
(
g
/
w
e
e
k
)
2
8
7
.
7
2
±
1
1
9
.
1
2
2
5
3
.
9
5
±
1
2
3
.
6
5
0
.
0
1
2
W
h
i
l
e
n
o
a
g
e
d
i
f
f
e
r
e
n
c
e
w
as
d
e
t
ec
t
e
d
d
u
e
t
o
t
h
e
m
atch
in
g
p
ar
am
eter
s
,
e
d
u
c
a
t
i
o
n
a
l
l
e
v
e
l
w
a
s
s
i
g
n
i
f
i
c
a
n
t
l
y
l
o
w
e
r
a
m
o
n
g
c
a
s
e
s
.
I
t
h
a
s
b
e
e
n
d
e
m
o
n
s
t
r
a
t
e
d
th
a
t
a
h
i
g
h
e
r
e
d
u
c
a
t
i
o
n
l
e
v
e
l
i
s
c
o
r
r
e
l
a
t
e
d
w
it
h
a
b
e
t
t
e
r
a
c
c
es
s
t
o
i
n
f
o
r
m
a
t
i
o
n
an
d
g
r
e
a
t
e
r
a
w
a
r
e
n
e
s
s
o
f
r
i
s
k
f
a
c
t
o
r
s
,
f
u
r
t
h
e
r
m
o
r
e
,
a
h
i
g
h
e
r
e
d
u
c
a
t
i
o
n
a
l
l
e
v
e
l
is
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t J Pu
b
lic
Hea
lth
Sci
I
SS
N:
2252
-
8
8
0
6
R
ela
tio
n
s
h
ip
b
etw
ee
n
s
h
ift w
o
r
k
a
n
d
th
e
r
is
k
o
f c
o
lo
r
ec
ta
l c
a
n
ce
r
a
mo
n
g
M
o
r
o
cc
a
n
…
(
Ha
mza
E
lb
a
ylek
)
1113
a
s
s
o
ci
a
t
e
d
w
it
h
g
r
e
a
t
e
r
a
c
c
e
p
ta
n
c
e
o
f
c
o
l
o
n
o
s
c
o
p
y
a
s
a
p
r
ev
e
n
t
i
v
e
m
e
as
u
r
e
[
2
8
]
.
I
n
l
i
n
e
w
i
t
h
o
u
r
f
i
n
d
i
n
g
s
,
m
a
r
i
t
a
l
s
t
a
t
u
s
i
s
as
s
o
c
ia
t
e
d
w
ith
r
i
s
k
o
f
C
R
C
,
d
u
e
t
o
r
e
p
r
o
d
u
c
t
i
v
e
a
n
d
s
e
x
h
o
r
m
o
n
e
s
s
u
c
h
a
s
e
s
t
r
o
g
e
n
,
w
h
i
c
h
m
a
y
h
a
v
e
a
p
r
o
t
e
c
t
i
v
e
e
f
f
e
c
t
a
g
a
i
n
s
t
C
R
C
b
y
r
e
g
u
l
a
t
i
n
g
b
i
l
e
a
c
i
d
s
[
2
9
]
.
F
o
r
r
e
s
i
d
e
n
c
y
a
r
ea
,
C
R
C
is
t
y
p
i
c
al
l
y
c
o
n
s
i
d
e
r
e
d
a
s
a
n
u
r
b
a
n
c
a
n
c
e
r
,
o
f
t
e
n
l
i
n
k
e
d
t
o
a
n
u
r
b
a
n
l
i
f
e
s
ty
l
e
,
p
a
r
a
d
o
x
i
c
a
l
l
y
,
i
n
o
u
r
s
t
u
d
y
n
e
a
r
l
y
t
h
e
h
a
l
f
o
f
c
a
s
es
w
e
r
e
f
r
o
m
r
u
r
a
l
a
r
e
a
s
.
I
n
M
o
r
o
c
c
o
,
l
i
v
i
n
g
i
n
r
u
r
a
l
a
r
e
a
s
i
s
o
f
t
e
n
a
s
s
o
c
i
at
e
d
w
i
t
h
a
l
i
m
i
t
e
d
a
c
c
es
s
t
o
h
e
a
l
t
h
c
a
r
e
s
e
r
v
i
c
es
,
as
w
el
l
as
h
i
g
h
e
r
l
e
v
e
l
s
o
f
p
o
l
l
u
t
i
o
n
a
n
d
co
n
t
a
m
i
n
a
t
i
o
n
d
u
e
t
o
we
a
k
s
a
n
i
ta
t
i
o
n
i
n
f
r
a
s
t
r
u
c
t
u
r
e
.
M
o
r
e
o
v
e
r
,
p
e
o
p
l
e
i
n
r
u
r
a
l
a
r
ea
s
te
n
d
t
o
h
a
v
e
a
l
o
w
e
r
e
d
u
c
a
t
i
o
n
a
l
l
e
v
el
.
As
m
e
n
t
i
o
n
e
d
e
a
r
l
i
e
r
,
B
M
I
a
n
d
p
h
y
s
i
c
a
l
a
c
t
i
v
i
t
y
a
r
e
s
t
r
o
n
g
l
y
r
e
la
t
e
d
t
o
C
R
C
r
is
k
,
wi
t
h
s
u
b
s
t
a
n
ti
a
l
e
v
i
d
e
n
c
e
s
u
p
p
o
r
t
i
n
g
t
h
is
r
e
l
a
ti
o
n
s
h
ip
[
5
]
.
3
.
2
.
Sh
if
t
wo
r
k
a
nd
co
lo
re
c
t
a
l c
a
ncer
risk
a
cc
o
rding
to
l
o
ca
t
io
n a
nd
a
g
e
ca
t
eg
o
ries
T
a
b
l
e
2
p
r
e
s
e
n
t
s
t
h
e
c
r
u
d
e
a
n
d
a
d
j
u
s
t
e
d
O
R
a
n
d
9
5
%
C
I
f
o
r
a
l
l
t
y
p
e
s
o
f
s
h
i
f
t
w
o
r
k
i
n
r
e
l
a
t
io
n
t
o
C
R
C
r
i
s
k
,
w
it
h
s
i
g
n
i
f
i
c
a
n
t
g
e
n
e
r
al
ch
a
r
a
c
t
e
r
is
t
i
cs
c
o
n
s
i
d
e
r
e
d
a
s
c
o
n
f
o
u
n
d
i
n
g
f
a
c
t
o
r
s
.
R
o
t
at
i
n
g
s
h
i
f
t
w
o
r
k
s
h
o
w
e
d
a
s
i
g
n
i
f
i
c
a
n
t
i
n
c
r
e
a
s
e
i
n
C
R
C
r
i
s
k
i
n
t
h
e
c
r
u
d
e
m
o
d
e
l
(
O
R
a
:
1
.
7
6
;
9
5
%
C
I
:
1
.
0
6
-
2
.
9
3
)
,
a
f
t
e
r
a
d
j
u
s
t
i
n
g
f
o
r
c
o
n
f
o
u
n
d
i
n
g
f
a
c
t
o
r
s
t
h
e
r
i
s
k
wa
s
s
l
i
g
h
t
l
y
a
tt
e
n
u
a
t
e
d
b
u
t
r
e
m
ai
n
e
d
s
t
a
ti
s
t
i
c
al
l
y
s
i
g
n
i
f
i
c
a
n
t
(
OR
b
:
1
.
7
4
;
9
5
%
C
I
:
1
.
0
5
-
2
.
9
1
)
,
w
i
t
h
r
e
s
p
e
c
t
i
v
e
l
y
p
-
v
a
l
u
e
=
0
.
0
2
9
f
o
r
t
h
e
c
r
u
d
e
m
o
d
e
l
a
n
d
p
-
v
a
l
u
e
=
0
.
0
1
f
o
r
t
h
e
a
d
j
u
s
t
e
d
m
o
d
e
l
.
N
i
g
h
t
s
h
i
f
t
w
o
r
k
w
a
s
c
o
r
r
e
l
at
ed
w
i
t
h
a
s
l
i
g
h
t
i
n
c
r
e
a
s
e
o
f
C
R
C
r
i
s
k
b
u
t
t
h
i
s
w
as
n
o
t
s
t
a
t
is
ti
ca
l
l
y
s
i
g
n
i
f
i
ca
n
t
O
R
b
:
1
.
0
8
;
9
5
%
C
I
:
0
.
6
2
-
1
.
9
2
(
p
-
v
a
l
u
e
=
0
.
7
5
)
.
D
u
r
i
n
g
o
u
r
s
t
u
d
y
,
w
e
a
l
s
o
e
x
a
m
i
n
e
d
t
h
e
c
u
m
u
l
a
t
i
v
e
e
f
f
e
c
t
o
f
s
h
i
f
t
w
o
r
k
,
e
v
a
l
u
a
t
e
d
b
y
q
u
a
r
t
i
l
e
s
,
f
o
r
c
u
m
u
l
a
t
i
v
e
y
e
a
r
s
o
f
r
o
t
a
t
i
n
g
s
h
i
f
t
w
o
r
k
,
o
n
l
y
t
h
e
s
e
c
o
n
d
q
u
a
r
t
i
l
e
(
≤
8
-
1
3
<
)
w
a
s
a
s
s
o
ci
a
t
e
d
s
i
g
n
i
f
i
c
a
n
tl
y
w
i
t
h
a
h
i
g
h
e
r
r
i
s
k
o
f
C
R
C
i
n
b
o
t
h
c
r
u
d
e
O
R
a
:
2
.
2
3
;
9
5
%
C
I
:
1
.
1
1
-
4
.
4
7
(
p
-
v
a
l
u
e
=
0
.
0
2
2
)
a
n
d
a
d
j
u
s
t
e
d
m
o
d
e
l
s
OR
b
:
2
.
2
3
;
9
5
%
C
I
:
1
.
0
9
-
4
.
4
7
(
p
-
v
a
l
u
e
=
0
.
0
1
2
)
w
h
e
n
c
o
m
p
a
r
e
d
t
o
d
a
y
s
h
i
f
t
w
o
r
k
e
r
s
,
o
t
h
e
r
q
u
a
r
t
i
l
e
s
d
i
d
n
o
t
s
h
o
w
a
s
i
g
n
i
f
i
c
a
n
t
c
o
r
r
e
la
t
i
o
n
w
i
t
h
C
R
C
r
is
k
.
S
i
m
il
a
r
l
y
,
n
o
s
i
g
n
i
f
ic
a
n
t
ass
o
c
i
a
t
i
o
n
wa
s
f
o
u
n
d
b
e
t
w
e
e
n
c
u
m
u
l
a
ti
v
e
y
e
a
r
s
o
f
n
ig
h
t
s
h
i
f
t
w
o
r
k
a
n
d
C
R
C
r
is
k
a
cr
o
s
s
a
ll
q
u
a
r
t
i
le
s
.
T
ab
le
2
.
T
h
e
esti
m
ated
OR
an
d
C
I
9
5
% f
o
r
d
if
f
er
e
n
t sh
if
t w
o
r
k
s
with
co
lo
r
ec
tal
ca
n
ce
r
r
is
k
Y
e
a
r
s
o
f
w
o
r
k
C
a
ses
N
(
%)
C
o
n
t
r
o
l
s
N
(
%)
OR
a
(
C
I
9
5
%)
OR
b
(
C
I
9
5
%)
D
a
y
s
h
i
f
t
w
o
r
k
(
R
e
f
)
7
8
(
4
7
.
2
)
9
3
(
5
6
.
3
)
1
.
0
0
1
.
0
0
R
o
t
a
t
i
n
g
sh
i
f
t
w
o
r
k
5
6
(
3
3
.
9
)
3
8
(
2
3
)
1
.
7
6
(
1
.
0
6
-
2
.
9
3
)
1
.
7
4
(
1
.
0
5
-
2
.
9
1
)
p
-
v
a
l
u
e
0
.
0
2
9
0
.
0
1
N
i
g
h
t
sh
i
f
t
w
o
r
k
3
1
(
1
8
.
7
)
3
4
(
2
0
.
6
)
1
.
0
9
(
0
.
6
2
-
1
.
9
3
)
1
.
0
8
(
0
.
6
2
-
1
.
9
2
)
P
-
v
a
l
u
e
0
.
7
7
4
0
.
7
5
C
u
m
u
l
a
t
i
v
e
r
o
t
a
t
i
n
g
s
h
i
f
t
w
o
r
k
(
y
e
a
r
)
<8
1
4
(
2
5
)
1
1
(
2
8
.
9
)
1
.
5
2
(
0
.
6
5
-
3
.
5
4
)
1
.
5
0
(
0
.
6
5
-
3
.
4
3
)
p
-
v
a
l
u
e
0
.
3
3
1
0
.
2
5
≤8
-
<
13
2
8
(
5
0
)
1
5
(
3
9
.
4
)
2
.
2
3
(
1
.
1
1
-
4
.
4
7
)
2
.
2
3
(
1
.
0
9
-
4
.
4
7
)
P
-
v
a
l
u
e
0
.
0
2
2
0
.
0
1
2
≤
1
3
-
<
17
4
(
7
.
1
)
7
(
1
8
.
4
)
0
.
6
8
(
0
.
1
9
-
2
.
4
1
)
0
.
6
7
(
0
.
1
7
-
2
.
4
0
)
p
-
v
a
l
u
e
0
.
5
5
0
.
5
5
≥
1
7
1
0
(
1
7
.
8
)
5
(
8
.
9
)
2
.
3
8
(
0
.
7
8
-
7
.
2
6
)
2
.
3
5
(
0
.
7
7
-
7
.
2
4
)
P
-
v
a
l
u
e
0
.
1
1
7
0
.
1
2
8
C
u
m
u
l
a
t
i
v
e
n
i
g
h
t
sh
i
f
t
w
o
r
k
(
y
e
a
r
)
<2
7
(
2
2
.
5
)
1
1
(
3
2
.
3
)
0
.
7
6
(
0
.
2
8
-
2
.
0
5
)
0
.
7
5
(
0
.
2
6
-
2
.
0
2
)
p
-
v
a
l
u
e
0
.
5
8
5
0
.
5
5
7
≤2
-
<
5
1
0
(
3
2
.
2
)
9
(
2
6
.
4
)
1
.
3
2
(
0
.
5
1
-
3
.
4
1
)
1
.
2
9
(
0
.
5
1
-
3
.
4
0
)
P
-
v
a
l
u
e
0
.
5
6
0
.
4
2
≤5
-
<
8
6
(
1
9
.
3
)
1
0
(
2
9
.
4
)
0
.
7
2
(
0
.
2
5
-
2
.
0
7
)
0
.
7
1
(
0
.
2
4
-
2
.
0
7
)
p
-
v
a
l
u
e
0
.
5
3
2
0
.
5
≥8
8
(
2
5
.
8
)
4
(
1
1
.
7
)
2
.
3
8
(
0
.
6
9
-
8
.
2
0
)
2
.
3
6
(
0
.
6
7
-
8
.
1
9
)
p
-
v
a
l
u
e
0
.
1
5
7
0
.
1
OR
a
:
C
r
u
d
e
o
d
d
s
r
a
t
i
o
a
d
j
u
st
e
d
o
n
l
y
f
o
r
a
g
e
(
±
3
y
e
a
r
s)
,
OR
b
:
A
d
j
u
s
t
e
d
f
o
r
:
E
d
u
c
a
t
i
o
n
a
l
l
e
v
e
l
(
i
l
l
i
t
e
r
a
t
e
,
p
r
i
mar
y
,
s
e
c
o
n
d
a
r
y
,
u
n
i
v
e
r
si
t
y
)
;
R
e
s
i
d
e
n
c
y
(
u
r
b
a
n
,
r
u
r
a
l
)
;
M
a
r
t
i
a
l
st
a
t
u
s
(
n
e
v
e
r
m
a
r
r
i
e
d
,
m
a
r
r
i
e
d
,
d
i
v
o
r
c
e
d
,
w
i
d
o
w
e
d
)
;
B
M
I
(
u
n
d
e
r
w
e
i
g
h
t
,
n
o
r
m
a
l
,
o
v
e
r
w
e
i
g
h
t
,
o
b
e
s
i
t
y
)
;
P
h
y
si
c
a
l
a
c
t
i
v
i
t
y
(
l
o
w
,
m
o
d
e
r
a
t
e
,
h
i
g
h
)
;
To
t
a
l
e
n
e
r
g
y
i
n
t
a
k
e
(
K
c
a
l
)
c
o
n
t
i
n
u
o
u
s
v
a
r
i
a
b
l
e
;
F
i
b
e
r
I
n
t
a
k
e
(
g
/
d
a
y
)
c
o
n
t
i
n
u
o
u
s
v
a
r
i
a
b
l
e
;
C
a
l
c
i
u
m I
n
t
a
k
e
(
mg
/
d
a
y
)
c
o
n
t
i
n
u
o
u
s
v
a
r
i
a
b
l
e
;
R
e
d
me
a
t
i
n
t
a
k
e
(
g
/
w
e
e
k
)
c
o
n
t
i
n
u
o
u
s
v
a
r
i
a
b
l
e
.
I
n
r
e
s
p
e
ct
w
ith
o
u
r
f
in
d
in
g
s
,
a
Sp
an
i
s
h
p
o
p
u
l
at
io
n
-
b
a
s
ed
s
tu
d
y
,
in
d
ica
te
s
th
a
t
r
o
ta
ti
n
g
s
h
if
t
wo
r
k
wa
s
p
o
s
it
iv
e
ly
co
r
r
e
la
ted
w
ith
C
R
C
r
i
s
k
O
R
:
1
.
2
2
;
9
5
%
C
I
:
1
.
0
4
-
1
.
4
3
co
m
p
ar
ed
to
d
ay
s
h
if
t
wo
r
k
er
s
,
wh
il
e
n
ig
h
t
s
h
if
t
wo
r
k
wa
s
n
o
t
f
o
u
n
d
to
b
e
c
o
r
r
e
la
ted
w
ith
C
R
C
r
i
s
k
O
R
:0
.
7
9
;
9
5
%
C
I
: 0
.
6
2
-
1
.
0
0
.
Mo
r
eo
v
e
r
,
2
0
to
3
4
y
ea
r
s
o
f
c
u
m
u
l
at
iv
e
r
o
t
at
i
n
g
s
h
if
t
wo
r
k
wer
e
co
r
r
el
at
ed
wi
th
an
in
cr
ea
s
ed
r
i
s
k
o
f
C
R
C
,
al
th
o
u
g
h
,
in
o
u
r
s
t
u
d
y
o
n
ly
8
to
1
3
y
e
ar
s
o
f
c
u
m
u
la
t
iv
e
r
o
tat
in
g
s
h
i
f
t
w
o
r
k
s
h
o
w
ed
th
i
s
as
s
o
ci
at
io
n
[
1
6
]
.
I
n
co
n
tr
as
t
to
o
u
r
s
t
u
d
y
,
a
b
lac
k
w
o
m
en
’
s
co
h
o
r
t
s
t
u
d
y
f
o
u
n
d
a
h
ig
h
er
r
i
s
k
o
f
C
R
C
am
o
n
g
n
ig
h
t
s
h
if
t
wo
r
k
er
s
w
i
th
o
v
er
1
0
y
ea
r
s
o
f
ex
p
o
s
u
r
e
,
w
i
th
H
R
:
1
.
6
4
;
9
5
%
C
I
:
1
.
0
1
-
2
.
6
6
,
w
h
il
e
o
u
r
s
tu
d
y
s
h
o
wed
n
o
c
o
r
r
el
at
io
n
b
e
t
wee
n
cu
m
u
l
at
iv
e
y
ea
r
s
o
f
n
ig
h
t
s
h
i
f
t
w
o
r
k
an
d
th
e
r
i
s
k
o
f
C
R
C
o
v
er
a
ll
[
3
0
]
.
W
h
en
s
t
r
a
tif
ied
b
y
tu
m
o
r
lo
ca
tio
n
,
n
ig
h
t
s
h
if
t
wo
r
k
wa
s
p
o
s
it
iv
e
ly
co
r
r
el
at
ed
w
it
h
th
e
r
i
s
k
o
f
r
ec
t
al
ca
n
ce
r
in
th
e
ad
ju
s
t
ed
m
o
d
el
O
R
b
:
2
.
1
4
;
95%
C
I
:
1
.
0
4
-
4
.
4
2
(
p
-
v
alu
e
=
0
.
0
4
8
)
.
Ho
wev
er
,
f
o
r
co
lo
n
c
an
ce
r
r
o
ta
tin
g
s
h
if
t
wo
r
k
e
r
s
s
h
o
wed
a
b
o
r
d
er
lin
e
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8
8
0
6
I
n
t J Pu
b
lic
Hea
lth
Sci
,
Vo
l.
14
,
No
.
3
,
Sep
tem
b
er
20
25
:
1
1
0
9
-
1
1
1
8
1114
non
-
s
ig
n
if
i
ca
n
t
in
cr
e
a
s
e
in
C
R
C
r
i
s
k
O
R
b
:
1
.
6
2
;
9
5
%
C
I
:
0
.
9
6
-
2
.
6
8
a
s
s
h
o
wn
in
T
ab
le
3
.
S
im
i
la
r
ly
,
a
C
an
ad
ian
ca
s
e
-
co
n
tr
o
l
s
tu
d
y
f
o
cu
s
in
g
o
n
m
en
s
h
o
we
d
th
at
p
er
m
an
en
t
n
ig
h
t
s
h
if
t
wo
r
k
er
s
h
ad
t
w
ice
th
e
r
i
s
k
th
an
d
ay
s
h
i
f
t
wo
r
k
er
s
f
o
r
co
l
o
n
ca
n
ce
r
O
R
:
2
.
0
3
;
9
5
%
C
I
:
1
.
4
3
-
2
.
8
9
an
d
r
ec
ta
l
c
an
ce
r
O
R
:
2
.
0
9
;
9
5
%
C
I
:
1
.
4
0
-
3
.
1
4
[
3
1
]
.
Me
an
wh
il
e,
a
ca
s
e
-
co
n
t
r
o
l
s
tu
d
y
o
f
Au
s
t
r
a
li
an
wo
m
en
f
o
u
n
d
n
o
co
r
r
e
la
tio
n
b
et
we
en
r
o
ta
tin
g
s
h
if
t
wo
r
k
an
d
th
e
r
i
s
k
o
f
co
lo
n
a
n
d
r
ec
ta
l
ca
n
ce
r
[
1
7
]
.
Mo
r
eo
v
er
,
a
r
ec
en
t
m
et
a
-
an
al
y
s
i
s
s
h
o
w
ed
a
b
o
r
d
er
lin
e
r
i
s
k
o
f
C
R
C
o
n
n
ig
h
t
s
h
i
f
t
wo
r
k
er
s
b
u
t
n
o
n
-
s
i
g
n
if
i
ca
ti
v
e
O
R
:
1
.
0
1
;
9
5
%
C
I
:
0
.
9
6
-
1
.
0
6
[
3
2
]
.
W
h
en
s
t
r
at
if
ied
b
y
ag
e
g
r
o
u
p
s
,
r
o
t
at
in
g
s
h
if
t
wo
r
k
s
h
o
w
ed
a
p
o
s
it
iv
e
n
o
n
-
s
ig
n
if
ic
an
t
co
r
r
el
at
io
n
wi
th
C
R
C
r
i
s
k
f
o
r
p
eo
p
le
ag
ed
b
et
we
en
4
5
-
6
5
O
R
a
:
2
.
1
2
;
9
5
%
C
I
:
0
.
9
5
-
4
.
7
5
,
af
ter
ad
ju
s
t
in
g
f
o
r
c
o
n
f
o
u
n
d
in
g
f
a
cto
r
s
,
th
e
r
i
s
k
o
f
C
R
C
b
ec
a
m
e
s
i
g
n
if
i
ca
n
t
O
R
b
:2
.
1
8
C
I
9
5
%
:
1
.
0
3
-
4
.
4
9
(
p
-
v
alu
e
=
0
.
0
4
2
)
.
W
h
il
e
n
o
a
s
s
o
cia
t
io
n
wa
s
o
b
s
er
v
ed
ac
r
o
s
s
th
e
o
th
er
ag
e
ca
teg
o
r
i
es
a
s
s
h
o
wn
in
T
ab
le
4
.
I
n
co
n
tr
as
t,
o
th
er
s
t
u
d
i
es
h
av
e
s
u
g
g
e
s
te
d
th
a
t
t
h
e
r
i
s
k
o
f
th
e
s
e
m
o
d
if
iab
le
r
i
s
k
f
ac
to
r
s
d
ec
r
ea
s
e
s
af
t
er
r
et
ir
e
m
en
t,
wh
en
s
h
if
t
wo
r
k
e
r
s
r
e
s
u
m
e
a
n
o
r
m
a
l
lif
e
s
ty
le
w
ith
r
e
g
u
l
ar
m
ea
l
an
d
s
le
ep
s
c
h
ed
u
le
[
1
7
]
,
[
3
3
]
.
I
n
a
S
wed
i
s
h
c
o
h
o
r
t
s
tu
d
y
o
f
ap
p
r
o
x
i
m
a
te
ly
3
.
5
m
il
l
io
n
p
ar
ti
cip
an
t
s
an
d
1
9
y
e
ar
s
f
o
ll
o
w
-
u
p
,
s
h
o
wed
n
o
a
s
s
o
cia
t
io
n
b
et
we
en
s
h
if
t
wo
r
k
a
n
d
th
e
r
i
s
k
o
f
C
R
C
f
o
r
b
o
th
m
en
an
d
wo
m
en
,
m
o
r
eo
v
er
,
an
o
th
er
co
h
o
r
t
s
tu
d
y
a
ls
o
f
o
u
n
d
n
o
co
r
r
e
la
tio
n
b
e
t
w
ee
n
s
h
if
t
wo
r
k
an
d
C
R
C
in
J
a
p
an
[
2
]
,
[
3
4
]
.
T
ab
le
3
.
T
h
e
esti
m
ated
OR
an
d
C
I
9
5
% f
o
r
d
if
f
er
e
n
t sh
if
t w
o
r
k
s
with
co
lo
r
ec
tal
ca
n
ce
r
r
is
k
b
y
tu
m
o
r
lo
ca
tio
n
Lo
c
a
t
i
o
n
C
o
l
o
n
R
e
c
t
a
l
C
o
l
o
r
e
c
t
a
l
o
v
e
r
a
l
l
OR
a
(
C
I
9
5
%)
OR
b
(
C
I
9
5
%)
OR
a
(
C
I
9
5
%)
OR
b
(
C
I
9
5
%)
OR
a
(
C
I
9
5
%)
OR
b
(
C
I
9
5
%)
C
a
ses
/
c
o
n
t
r
o
l
s
4
6
/
9
3
2
5
/
9
3
7
8
/
9
3
D
a
y
S
.
W
.
1
.
0
0
1
.
0
0
1
.
0
0
1
.
0
0
1
.
0
0
1
.
0
0
C
a
ses
/
c
o
n
t
r
o
l
s
3
1
/
3
8
1
7
/
3
8
5
6
/
3
8
R
o
t
a
t
i
n
g
S
.
W
.
1
.
6
5
(
0
.
9
1
-
2
.
9
8
)
1
.
6
9
(
0
.
9
6
-
2
.
9
8
)
1
.
6
6
(
0
.
8
1
-
3
.
4
2
)
1
.
6
2
(
0
.
7
5
-
3
.
3
9
)
1
.
7
6
(
1
.
0
6
-
2
.
9
3
)
1
.
7
4
(
1
.
0
5
-
2
.
9
1
)
C
a
ses
/
c
o
n
t
r
o
l
s
1
0
/
3
4
2
0
/
3
4
3
1
/
3
4
N
i
g
h
t
S
.
W
.
0
.
5
9
(
0
.
2
7
-
1
.
3
)
0
.
6
5
(
0
.
3
4
-
1
.
3
4
)
2
.
1
9
(
1
.
0
8
-
4
.
4
4
)
2
.
1
4
(
1
.
0
4
-
4
.
4
2
)
1
.
0
9
(
0
.
6
2
-
1
.
9
3
)
1
.
0
8
(
0
.
6
2
-
1
.
9
2
)
P
-
v
a
l
u
e
0
.
0
4
6
0
.
0
5
8
0
.
0
7
5
0
.
0
4
8
0
.
0
6
2
0
.
0
4
4
OR
a
:
C
r
u
d
e
o
d
d
s ra
t
i
o
a
d
j
u
s
t
e
d
o
n
l
y
f
o
r
a
g
e
(
±
3
y
e
a
r
s)
,
OR
b
:
A
d
j
u
st
e
d
f
o
r
:
Ed
u
c
a
t
i
o
n
a
l
l
e
v
e
l
(
i
l
l
i
t
e
r
a
t
e
,
p
r
i
mar
y
,
sec
o
n
d
a
r
y
,
u
n
i
v
e
r
si
t
y
)
;
R
e
si
d
e
n
c
y
(
u
r
b
a
n
,
r
u
r
a
l
)
;
M
a
r
t
i
a
l
st
a
t
u
s
(
n
e
v
e
r
m
a
r
r
i
e
d
,
marr
i
e
d
,
d
i
v
o
r
c
e
d
,
w
i
d
o
w
e
d
)
;
B
M
I
(
u
n
d
e
r
w
e
i
g
h
t
,
n
o
r
m
a
l
,
o
v
e
r
w
e
i
g
h
t
,
o
b
e
si
t
y
)
;
P
h
y
s
i
c
a
l
a
c
t
i
v
i
t
y
(
l
o
w
,
m
o
d
e
r
a
t
e
,
h
i
g
h
)
;
To
t
a
l
e
n
e
r
g
y
i
n
t
a
k
e
(
K
c
a
l
)
c
o
n
t
i
n
u
o
u
s
v
a
r
i
a
b
l
e
;
F
i
b
e
r
I
n
t
a
k
e
(
g
/
d
a
y
)
c
o
n
t
i
n
u
o
u
s
v
a
r
i
a
b
l
e
;
C
a
l
c
i
u
m
I
n
t
a
k
e
(
mg
/
d
a
y
)
c
o
n
t
i
n
u
o
u
s
v
a
r
i
a
b
l
e
;
R
e
d
me
a
t
i
n
t
a
k
e
(
g
/
w
e
e
k
)
c
o
n
t
i
n
u
o
u
s
v
a
r
i
a
b
l
e
.
8
7
c
o
l
o
n
c
a
n
c
e
r
c
a
ses
a
n
d
6
2
r
e
c
t
a
l
c
a
n
c
e
r
c
a
s
e
s a
r
e
l
e
ss
t
h
a
n
1
6
5
d
u
e
t
o
u
n
k
n
o
w
n
l
o
c
a
t
i
o
n
(
n
=
1
6
)
.
S
.
W
:
S
h
i
f
t
w
o
r
k
.
T
ab
le
4
.
T
h
e
esti
m
ated
OR
an
d
C
I
9
5
% f
o
r
d
if
f
er
e
n
t sh
if
t w
o
r
k
s
with
co
lo
r
ec
tal
ca
n
ce
r
r
is
k
b
y
ag
e
ca
teg
o
r
ies
A
g
e
C
a
t
e
g
o
r
y
F
r
o
m
2
5
t
o
l
e
ss
t
h
a
n
4
5
F
r
o
m
4
5
t
o
l
e
ss
t
h
a
n
6
5
F
r
o
m
6
5
t
o
8
5
OR
a
(
C
I
9
5
%)
OR
b
(
C
I
9
5
%)
OR
a
(
C
I
9
5
%)
OR
b
(
C
I
9
5
%)
OR
a
(
C
I
9
5
%)
OR
b
(
C
I
9
5
%)
C
a
ses
/
c
o
n
t
r
o
l
s
1
9
/
2
2
2
5
/
4
3
3
4
/
2
8
D
a
y
S
.
W
.
1
.
0
0
1
.
0
0
1
.
0
0
1
.
0
0
1
.
0
0
1
.
0
0
C
a
ses
/
c
o
n
t
r
o
l
s
1
6
/
9
2
1
/
1
7
1
9
/
1
2
R
o
t
a
t
i
n
g
S
.
W
.
2
.
0
6
(
0
.
7
4
-
5
.
7
2
)
2
.
1
3
(
0
.
8
5
-
5
.
8
3
)
2
.
1
2
(
0
.
9
5
-
4
.
7
5
)
2
.
1
8
(
1
.
0
3
-
4
.
7
9
)
1
.
3
(
0
.
5
4
-
3
.
1
3
)
1
.
2
7
(
0
.
4
9
-
3
.
1
1
)
C
a
ses
/
c
o
n
t
r
o
l
s
1
4
/
1
1
1
1
/
1
5
6
/
8
N
i
g
h
t
S
.
W
.
1
.
4
7
(
0
.
5
4
-
4)
1
.
4
2
(
0
.
5
9
-
4
.
0
5
)
1
.
2
6
(
0
.
5
-
3
.
1
7
)
1
.
3
(
0
.
5
4
-
3
.
2
1
)
0
.
6
2
(
0
.
1
9
-
2)
0
.
5
9
(
0
.
1
7
-
1
.
9
8
)
P
-
v
a
l
u
e
0
.
3
6
5
0
.
3
8
2
0
.
0
3
3
0
.
0
4
2
0
.
5
1
3
0
.
5
0
2
OR
a
:
C
r
u
d
e
o
d
d
s ra
t
i
o
a
d
j
u
s
t
e
d
o
n
l
y
f
o
r
a
g
e
(
±
3
y
e
a
r
s)
,
OR
b
:
A
d
j
u
st
e
d
f
o
r
:
Ed
u
c
a
t
i
o
n
a
l
l
e
v
e
l
(
i
l
l
i
t
e
r
a
t
e
,
p
r
i
mar
y
,
sec
o
n
d
a
r
y
,
u
n
i
v
e
r
si
t
y
)
;
R
e
si
d
e
n
c
y
(
u
r
b
a
n
,
r
u
r
a
l
)
;
M
a
r
t
i
a
l
st
a
t
u
s
(
n
e
v
e
r
m
a
r
r
i
e
d
,
marr
i
e
d
,
d
i
v
o
r
c
e
d
,
w
i
d
o
w
e
d
)
;
B
M
I
(
u
n
d
e
r
w
e
i
g
h
t
,
n
o
r
m
a
l
,
o
v
e
r
w
e
i
g
h
t
,
o
b
e
si
t
y
)
;
P
h
y
s
i
c
a
l
a
c
t
i
v
i
t
y
(
l
o
w
,
m
o
d
e
r
a
t
e
,
h
i
g
h
)
;
To
t
a
l
e
n
e
r
g
y
i
n
t
a
k
e
(
K
c
a
l
)
c
o
n
t
i
n
u
o
u
s
v
a
r
i
a
b
l
e
;
F
i
b
e
r
I
n
t
a
k
e
(
g
/
d
a
y
)
c
o
n
t
i
n
u
o
u
s
v
a
r
i
a
b
l
e
;
C
a
l
c
i
u
m I
n
t
a
k
e
(
m
g
/
d
a
y
)
c
o
n
t
i
n
u
o
u
s
v
a
r
i
a
b
l
e
;
R
e
d
m
e
a
t
i
n
t
a
k
e
(
g
/
w
e
e
k
)
c
o
n
t
i
n
u
o
u
s
v
a
r
i
a
b
l
e
.
S
.
W
:
S
h
i
f
t
w
o
r
k
.
3
.
3
.
Ca
rc
ino
g
enesis
o
f
ro
t
a
t
i
o
na
l a
nd
nig
ht
s
hift
o
f
wo
rk
Sev
er
a
l
h
y
p
o
th
e
s
e
s
h
av
e
b
e
en
ad
v
an
ce
d
to
ex
p
l
ai
n
th
e
ca
r
c
in
o
g
en
ic
p
o
ten
ti
al
o
f
r
o
t
at
in
g
an
d
n
ig
h
t
s
h
if
t
w
o
r
k
.
T
wo
o
f
th
e
s
e
r
em
ain
th
e
s
tr
o
n
g
es
t,
t
h
e
f
i
r
s
t
s
u
g
g
es
t
s
th
a
t
r
o
t
at
in
g
an
d
n
ig
h
t
s
h
if
t
wo
r
k
e
r
s
ad
h
er
e
m
o
r
e
to
a
n
u
n
h
ea
lt
h
y
li
f
e
s
t
y
l
e
,
co
n
s
u
m
in
g
m
ai
n
ly
f
a
s
t
f
o
o
d
an
d
en
er
g
y
-
d
en
s
e
f
o
o
d
s
d
u
e
t
o
th
e
ch
al
len
g
es
of
m
ain
ta
in
in
g
a
h
e
al
th
y
d
ie
t
w
it
h
th
e
ir
wo
r
k
s
ch
ed
u
le
s
[
3
5
]
.
S
h
if
t
wo
r
k
er
s
a
ls
o
h
av
e
le
s
s
r
e
cr
ea
t
io
n
a
l
p
h
y
s
i
ca
l
ac
t
iv
ity
t
h
an
th
e
g
en
er
al
p
o
p
u
la
tio
n
[
3
6
]
,
wh
ich
p
l
ac
es
s
h
if
t
wo
r
k
er
s
a
t
an
el
ev
a
ted
r
i
s
k
f
o
r
b
o
t
h
ty
p
e
I
I
d
iab
et
es
an
d
o
b
e
s
i
ty
[
3
7
]
,
b
o
t
h
o
f
wh
ich
r
ec
o
g
n
iz
ed
r
i
s
k
f
a
cto
r
s
f
o
r
C
R
C
[
3
8
]
.
I
n
a
wo
m
en
’
s
co
h
o
r
t
s
tu
d
y
,
r
o
ta
tin
g
an
d
n
ig
h
t
s
h
if
t
wo
r
k
er
s
wer
e
m
o
r
e
lik
ely
to
b
e
s
m
o
k
e
r
s
an
d
ex
h
ib
i
ted
a
h
i
g
h
er
r
i
s
k
o
f
C
R
C
co
m
p
ar
ed
to
d
ay
s
h
i
f
t
wo
r
k
e
r
s
,
wi
th
h
ig
h
er
ex
p
r
e
s
s
io
n
o
f
in
s
u
l
in
r
e
ce
p
to
r
s
u
b
s
tr
at
e
1
(
I
R
S1
)
an
d
I
R
S
2
,
wh
i
ch
p
r
o
m
o
te
ce
ll
p
r
o
l
if
er
a
t
io
n
an
d
in
s
u
lin
r
e
s
i
s
tan
ce
[
3
9
]
.
I
n
o
u
r
s
tu
d
y
,
cig
ar
e
tt
e
s
m
o
k
in
g
an
d
a
lco
h
o
l
co
n
s
u
m
p
t
io
n
wer
e
n
o
t
co
n
s
i
d
er
ed
d
u
e
t
o
th
e
s
o
c
io
cu
lt
u
r
al
c
o
n
t
ex
t
o
f
Mo
r
o
cc
o
,
w
h
e
r
e
th
eir
p
r
ev
al
en
c
e
am
o
n
g
wo
m
en
i
s
lo
w.
T
h
e
s
e
co
n
d
m
e
ch
an
i
s
m
i
s
c
ir
c
ad
i
an
r
h
y
th
m
d
i
s
r
u
p
t
io
n
.
Me
l
at
o
n
in
,
a
h
o
r
m
o
n
e
th
a
t
f
o
llo
w
s
a
f
lu
c
tu
a
ti
n
g
p
a
t
ter
n
w
ith
in
in
d
i
v
id
u
a
l
s
o
v
er
a
2
4
-
h
cy
c
le
,
r
e
a
ch
e
s
th
e
h
ig
h
es
t
lev
el
s
in
th
e
ab
s
en
c
e
o
f
l
ig
h
t
a
t
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t J Pu
b
lic
Hea
lth
Sci
I
SS
N:
2252
-
8
8
0
6
R
ela
tio
n
s
h
ip
b
etw
ee
n
s
h
ift w
o
r
k
a
n
d
th
e
r
is
k
o
f c
o
lo
r
ec
ta
l c
a
n
ce
r
a
mo
n
g
M
o
r
o
cc
a
n
…
(
Ha
mza
E
lb
a
ylek
)
1115
n
ig
h
t
.
H
o
w
ev
er
,
i
t
h
as
b
e
en
s
h
o
wn
th
a
t
r
o
ta
tin
g
an
d
n
ig
h
t
s
h
if
t
wo
r
k
er
s
h
av
e
lo
wer
lev
e
l
o
f
m
el
at
o
n
in
,
d
u
e
to
th
e
d
i
s
r
u
p
tio
n
o
f
it
s
p
r
o
d
u
ct
io
n
b
y
ar
tif
ic
ia
l
l
ig
h
t
d
u
r
in
g
n
i
g
h
t
s
h
i
f
t
s
[
4
0
]
,
[
4
1
]
.
Fu
r
t
h
er
m
o
r
e,
n
ig
h
t
s
h
if
t
wo
r
k
e
r
s
s
u
f
f
er
f
r
o
m
s
ig
n
if
ica
n
t
s
le
ep
d
ep
r
iv
a
tio
n
wi
th
an
av
er
a
g
e
o
f
8
.
3
h
o
f
s
le
ep
f
o
r
d
ay
s
h
if
t
wo
r
k
e
r
s
v
er
s
u
s
o
n
l
y
4
.
8
h
f
o
r
n
ig
h
t
s
h
if
t
wo
r
k
er
s
,
wh
ich
m
ay
r
e
s
u
l
t
in
a
lo
w
lev
el
o
f
m
el
ato
n
in
p
r
o
d
u
ct
io
n
[
4
2
]
.
A
p
r
ev
io
u
s
r
ev
i
ew
r
ep
o
r
t
ed
th
a
t
7
5
%
o
f
n
ig
h
t
s
h
if
t
wo
r
k
e
r
s
h
av
e
ir
r
eg
u
lar
m
e
la
to
n
in
r
h
y
th
m
s
[
4
3
]
.
Me
la
to
n
in
ex
er
ts
an
ti
ca
r
cin
o
g
en
ic
ef
f
ec
t
s
in
C
R
C
tu
m
o
r
g
r
o
wt
h
b
y
r
eg
u
l
at
in
g
tu
m
o
r
d
ev
elo
p
m
en
t
,
a
r
eg
u
lar
le
v
e
l
o
f
m
el
ato
n
in
m
ain
ta
in
s
h
o
m
eo
s
t
a
s
i
s
in
c
o
lo
r
ec
ta
l
t
i
s
s
u
e
s
[
4
4
]
.
M
o
r
eo
v
er
,
th
e
ci
r
ca
d
i
an
cy
cl
e
co
n
tr
o
l
s
m
et
ab
o
l
ic
p
r
o
ce
s
s
es
in
o
u
r
b
o
d
y
,
a
co
h
o
r
t
s
t
u
d
y
s
h
o
w
ed
t
h
at
c
ir
ca
d
ian
r
h
y
th
m
d
i
s
r
u
p
ti
o
n
co
u
ld
b
e
a
r
is
k
f
ac
to
r
f
o
r
co
lo
r
ec
ta
l
c
an
c
er
[
4
5
]
.
A
m
e
ta
b
o
l
ic
s
tu
d
y
o
f
c
i
r
ca
d
ian
cl
o
ck
p
ath
wa
y
g
en
e
s
id
en
t
if
i
ed
th
a
t
th
e
SN
P
r
s
3
7
4
3
6
9
9
7
in
R
O
R
A
m
ay
e
lev
at
e
th
e
r
is
k
o
f
d
ev
e
lo
p
in
g
co
lo
r
e
ct
al
ca
n
ce
r
[
4
6
]
.
Se
v
er
al
cir
ca
d
ian
g
en
e
s
m
ay
b
e
d
e
r
eg
u
la
ted
in
co
lo
n
ca
n
ce
r
c
el
l
lin
es
,
wh
i
ch
m
ay
p
r
o
m
o
te
ce
ll
p
r
o
l
if
er
a
tio
n
in
an
i
m
a
l
s
tu
d
ie
s
[
4
7
]
.
I
t
is
l
ik
e
ly
th
a
t
s
h
if
t
wo
r
k
ac
t
s
m
o
r
e
a
s
a
ca
n
c
er
p
r
o
m
o
ter
th
a
n
a
ca
n
ce
r
in
it
ia
to
r
[
4
8
]
.
I
n
th
is
s
tu
d
y
,
wo
r
k
er
s
w
er
e
d
ep
r
iv
ed
o
f
h
ea
lth
y
n
o
c
tu
r
n
a
l
s
leep
,
in
ad
d
it
io
n
r
ed
u
c
tio
n
o
f
m
el
ato
n
in
lev
e
l
d
u
e
to
ex
p
o
s
u
r
e
to
ar
tif
ic
ia
l
l
ig
h
t
in
f
ac
to
r
ie
s
.
R
o
ta
tio
n
al
s
h
if
t
wo
r
k
er
s
a
l
s
o
s
u
f
f
e
r
ed
f
r
o
m
th
e
d
i
s
r
u
p
t
io
n
s
o
f
th
e
c
ir
c
ad
i
an
r
h
y
th
m
ca
u
s
ed
b
y
a
lt
er
n
a
t
in
g
b
et
wee
n
th
e
d
ay
an
d
n
ig
h
t
s
h
if
t
s
.
A
lth
o
u
g
h
o
u
r
s
t
u
d
y
f
o
cu
s
e
d
o
n
ly
o
n
wo
m
en
,
wh
o
ar
e
k
n
o
wn
t
o
m
ai
n
t
ain
a
h
ea
lth
ier
lif
e
s
ty
le
,
7
5
%
o
f
s
h
if
t
wo
r
k
e
r
s
in
o
u
r
s
t
u
d
y
r
ep
o
r
ted
ir
r
eg
u
la
r
ea
tin
g
s
ch
ed
u
l
e
s
,
w
ith
s
o
m
e
ev
en
s
k
ip
p
in
g
m
e
al
s
,
an
d
av
o
id
in
g
p
h
y
s
i
ca
l
ac
ti
v
i
ty
.
Ou
r
s
tu
d
y
h
a
s
s
o
m
e
l
im
it
at
i
o
n
s
th
a
t
m
u
s
t
b
e
ac
k
n
o
w
led
g
ed
,
t
h
e
s
t
u
d
y
w
a
s
r
e
tr
o
s
p
ec
tiv
e
r
e
ly
in
g
o
n
th
e
m
em
o
r
y
o
f
th
e
p
ar
ti
cip
an
t
s
,
d
e
s
p
i
te
th
e
as
s
i
s
t
an
c
e
o
f
tr
a
in
ed
in
v
e
s
tig
ato
r
s
,
p
ar
ti
cip
a
n
t
s
m
ay
h
av
e
m
i
s
c
la
s
s
if
ie
d
th
em
s
elv
e
s
.
I
n
ad
d
i
tio
n
,
th
e
c
la
s
s
if
i
ca
tio
n
o
f
s
h
if
t
wo
r
k
v
ar
i
e
s
b
et
w
e
en
co
u
n
tr
ie
s
,
m
ak
in
g
d
ir
e
ct
c
o
m
p
ar
i
s
o
n
s
w
it
h
o
th
e
r
s
t
u
d
i
es
ch
a
ll
en
g
i
n
g
.
A
s
f
o
r
th
e
m
a
in
s
tr
en
g
th
s
o
f
th
i
s
s
tu
d
y
,
a
s
f
ar
a
s
w
e
k
n
o
w,
th
i
s
i
s
th
e
f
ir
s
t
Mo
r
o
c
ca
n
s
tu
d
y
to
a
s
s
e
s
s
s
h
if
t
wo
r
k
in
r
e
la
t
io
n
to
co
lo
r
e
ct
al
c
a
n
ce
r
r
i
s
k
.
T
h
e
s
tu
d
y
wa
s
co
n
d
u
ct
ed
a
t
C
H
U
Mo
h
a
m
ed
VI
,
r
an
k
ed
a
s
t
h
e
s
e
co
n
d
lar
g
es
t
h
o
s
p
it
al
in
Mo
r
o
cc
o
wh
i
ch
p
r
o
v
id
e
s
t
h
e
s
t
u
d
y
w
ith
a
lar
g
e
e
th
n
i
c
an
d
s
o
c
io
-
e
co
n
o
m
ic
d
iv
er
s
it
y
.
Mo
r
eo
v
er
,
s
h
i
f
t
wo
r
k
w
a
s
ev
alu
a
te
d
in
d
i
f
f
er
en
t
jo
b
s
f
r
o
m
v
ar
io
u
s
f
ie
ld
s
.
T
r
a
in
in
g
s
e
s
s
io
n
s
w
er
e
p
r
o
v
id
ed
to
in
v
e
s
t
ig
a
to
r
s
p
r
io
r
to
t
h
e
s
tu
d
y
to
en
h
an
c
e
q
u
al
ity
o
f
g
en
er
a
ted
d
a
ta,
an
d
m
in
im
iz
e
r
ec
a
l
l
b
ia
s
,
w
it
h
a
p
ilo
t
te
s
t
to
ev
a
lu
a
te
th
e
q
u
e
s
t
io
n
n
a
ir
e
an
d
m
ak
e
n
ec
e
s
s
a
r
y
ad
ju
s
t
m
en
t
s
.
4.
CO
NCLU
SI
O
N
T
h
e
f
in
d
in
g
s
f
r
o
m
th
i
s
s
tu
d
y
em
p
h
a
s
ize
th
e
p
o
ten
t
ia
l
i
n
f
lu
en
ce
o
f
r
o
ta
t
in
g
s
h
if
t
wo
r
k
in
in
c
r
ea
s
in
g
th
e
r
i
s
k
o
f
co
lo
r
ec
ta
l
ca
n
ce
r
am
o
n
g
M
o
r
o
c
ca
n
wo
m
en
,
af
f
e
ct
ed
b
y
th
e
d
u
r
at
io
n
o
f
s
h
if
t
wo
r
k
.
T
h
e
s
e
f
in
d
i
n
g
s
ar
e
co
n
s
i
s
ten
t
wi
th
o
b
s
er
v
at
io
n
s
f
r
o
m
d
ev
elo
p
ed
co
u
n
tr
ie
s
.
Ga
in
in
g
a
co
m
p
r
eh
en
s
iv
e
u
n
d
er
s
t
an
d
in
g
o
f
b
o
t
h
m
o
d
if
i
ab
le
an
d
n
o
n
-
m
o
d
if
ia
b
l
e
r
i
s
k
f
ac
to
r
s
o
f
co
lo
r
e
ct
al
c
an
c
er
w
il
l
b
e
v
alu
ab
l
e
f
o
r
f
u
tu
r
e
s
tu
d
i
es
i
n
M
o
r
o
c
co
an
d
No
r
t
h
Af
r
ican
co
u
n
tr
ie
s
,
g
iv
en
th
e
ir
s
o
ci
o
-
d
em
o
g
r
ap
h
i
c
s
i
m
i
lar
i
ti
es
.
Ad
d
i
ti
o
n
a
lly
,
s
h
if
t
wo
r
k
s
h
o
u
ld
b
e
co
n
s
i
d
er
ed
as
a
c
o
n
f
o
u
n
d
in
g
f
a
cto
r
in
f
u
tu
r
e
s
tu
d
ie
s
.
Mo
r
eo
v
er
,
th
e
d
ev
e
lo
p
m
en
t
o
f
b
et
ter
p
r
ev
en
tiv
e
s
tr
at
eg
i
e
s
f
o
r
s
h
i
f
t
wo
r
k
er
s
,
s
u
ch
as
p
r
o
m
o
tin
g
a
h
e
al
th
i
er
d
i
et
,
l
if
e
s
ty
l
e
an
d
s
l
ee
p
p
at
te
r
n
s
,
a
s
th
ey
a
r
e
at
an
el
ev
a
ted
r
i
s
k
f
o
r
c
o
lo
r
ec
ta
l c
an
c
er
.
ACK
NO
WL
E
DG
M
E
N
T
S
T
h
e
au
th
o
r
s
co
n
f
ir
m
th
at
t
h
ey
h
av
e
n
o
f
in
a
n
cial
in
ter
ests
,
s
u
ch
as
f
u
n
d
in
g
,
in
v
es
tm
en
ts
,
o
r
s
p
o
n
s
o
r
s
h
ip
s
,
th
at
co
u
ld
in
f
l
u
en
ce
th
e
co
n
ten
t
o
f
th
is
wo
r
k
.
T
h
ey
also
s
tate
th
at
th
ey
h
av
e
n
o
n
o
n
-
f
in
an
cial
in
ter
ests
,
s
u
ch
as
p
er
s
o
n
al
r
elatio
n
s
h
ip
s
,
af
f
iliatio
n
s
,
o
r
i
n
tellectu
al
b
iases
,
th
at
co
u
ld
cr
ea
te
a
co
n
f
lict.
Ad
d
itio
n
ally
,
th
ey
d
ec
lar
e
th
at
th
er
e
ar
e
n
o
co
m
p
etin
g
in
ter
e
s
ts
th
at
co
u
ld
af
f
ec
t
th
e
o
b
jectiv
ity
o
r
in
teg
r
ity
o
f
th
eir
r
esear
ch
.
F
UNDING
I
NF
O
R
M
A
T
I
O
N
T
h
e
au
t
h
o
r
s
c
o
n
f
ir
m
th
at
n
o
ex
ter
n
al
f
u
n
d
in
g
was
r
ec
eiv
ed
f
o
r
t
h
is
wo
r
k
.
T
h
ey
d
id
n
o
t
r
ec
ei
v
e
f
in
an
cial
s
u
p
p
o
r
t
f
r
o
m
an
y
o
r
g
an
izatio
n
,
in
s
titu
tio
n
,
o
r
in
d
iv
id
u
al.
Ad
d
itio
n
ally
,
th
er
e
wer
e
n
o
g
r
an
ts
,
s
p
o
n
s
o
r
s
h
ip
s
,
o
r
f
in
an
cial
co
n
t
r
ib
u
tio
n
s
th
at
in
f
l
u
en
ce
d
t
h
e
r
e
s
ea
r
ch
.
AUTHO
R
CO
NT
RI
B
UT
I
O
NS ST
A
T
E
M
E
N
T
T
h
is
jo
u
r
n
al
u
s
es
th
e
C
o
n
tr
ib
u
to
r
R
o
les
T
ax
o
n
o
m
y
(
C
R
ed
iT
)
to
r
ec
o
g
n
ize
in
d
iv
id
u
al
au
th
o
r
co
n
tr
ib
u
tio
n
s
,
r
ed
u
ce
au
th
o
r
s
h
ip
d
is
p
u
tes,
an
d
f
ac
ilit
ate
co
llab
o
r
atio
n
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8
8
0
6
I
n
t J Pu
b
lic
Hea
lth
Sci
,
Vo
l.
14
,
No
.
3
,
Sep
tem
b
er
20
25
:
1
1
0
9
-
1
1
1
8
1116
Na
m
e
o
f
Aut
ho
r
C
M
So
Va
Fo
I
R
D
O
E
Vi
Su
P
Fu
Ham
ze
E
lb
ay
lek
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
So
u
m
ia
Am
m
o
r
✓
✓
✓
✓
✓
✓
✓
✓
C
:
C
o
n
c
e
p
t
u
a
l
i
z
a
t
i
o
n
M
:
M
e
t
h
o
d
o
l
o
g
y
So
:
So
f
t
w
a
r
e
Va
:
Va
l
i
d
a
t
i
o
n
Fo
:
Fo
r
mal
a
n
a
l
y
s
i
s
I
:
I
n
v
e
s
t
i
g
a
t
i
o
n
R
:
R
e
so
u
r
c
e
s
D
:
D
a
t
a
C
u
r
a
t
i
o
n
O
:
W
r
i
t
i
n
g
-
O
r
i
g
i
n
a
l
D
r
a
f
t
E
:
W
r
i
t
i
n
g
-
R
e
v
i
e
w
&
E
d
i
t
i
n
g
Vi
:
Vi
su
a
l
i
z
a
t
i
o
n
Su
:
Su
p
e
r
v
i
s
i
o
n
P
:
P
r
o
j
e
c
t
a
d
mi
n
i
st
r
a
t
i
o
n
Fu
:
Fu
n
d
i
n
g
a
c
q
u
i
si
t
i
o
n
CO
NF
L
I
C
T
O
F
I
N
T
E
R
E
S
T
ST
A
T
E
M
E
NT
T
h
e
au
th
o
r
s
d
ec
lar
e
th
at
th
e
y
h
av
e
n
o
k
n
o
wn
f
i
n
an
cial,
p
er
s
o
n
al,
p
r
o
f
ess
io
n
al,
o
r
n
o
n
-
f
in
an
cial
co
m
p
etin
g
i
n
ter
ests
th
at
co
u
l
d
h
av
e
i
n
f
lu
en
ce
d
th
e
wo
r
k
p
r
esen
ted
in
th
is
p
a
p
er
.
T
h
er
e
ar
e
n
o
ex
ter
n
al
f
u
n
d
in
g
s
o
u
r
ce
s
,
af
f
iliatio
n
s
,
o
r
r
elatio
n
s
h
ip
s
th
at
co
u
ld
b
e
p
er
ce
iv
ed
as
a
co
n
f
lict
o
f
in
t
er
est.
Fu
r
th
er
m
o
r
e,
th
e
au
th
o
r
s
af
f
ir
m
th
at
th
er
e
ar
e
n
o
p
o
liti
ca
l,
r
elig
io
u
s
,
id
e
o
lo
g
ical,
ac
a
d
em
ic,
o
r
i
n
tellectu
al
in
ter
ests
th
at
co
u
ld
h
av
e
a
f
f
ec
ted
th
e
o
b
jec
tiv
ity
o
r
in
teg
r
ity
o
f
th
e
r
esear
ch
.
T
h
e
r
esear
c
h
was
co
n
d
u
c
ted
in
d
e
p
en
d
e
n
tly
,
with
o
u
t a
n
y
b
ias o
r
ex
ter
n
al
in
f
lu
en
ce
,
en
s
u
r
in
g
f
air
an
d
o
b
je
ctiv
e
d
ec
is
io
n
-
m
ak
in
g
th
r
o
u
g
h
o
u
t th
e
s
tu
d
y
.
I
NF
O
RM
E
D
CO
NS
E
N
T
T
h
e
w
e
h
av
e
o
b
tain
e
d
in
f
o
r
m
ed
co
n
s
en
t
f
r
o
m
all
in
d
iv
id
u
al
s
in
clu
d
ed
in
th
is
s
tu
d
y
.
E
ac
h
p
ar
ticip
an
t
was
f
u
lly
in
f
o
r
m
e
d
ab
o
u
t
t
h
e
p
u
r
p
o
s
e,
p
r
o
ce
d
u
r
es,
an
d
p
o
te
n
tial
r
is
k
s
o
f
th
e
r
esear
c
h
.
W
r
i
tten
p
er
m
is
s
io
n
was
o
b
tain
ed
p
r
io
r
to
th
eir
in
clu
s
io
n
,
en
s
u
r
in
g
th
eir
v
o
lu
n
tar
y
p
ar
ticip
atio
n
an
d
u
n
d
er
s
tan
d
in
g
o
f
th
e
s
tu
d
y
with
r
esp
ec
t o
f
p
r
iv
ac
y
.
E
T
H
I
CAL AP
P
RO
V
AL
T
h
is
s
tu
d
y
i
n
v
o
lv
i
n
g
h
u
m
a
n
p
ar
ticip
an
ts
was
co
n
d
u
cted
i
n
co
m
p
lian
ce
with
all
r
elev
a
n
t
n
atio
n
al
r
eg
u
latio
n
s
an
d
in
s
titu
tio
n
al
p
o
licies,
f
o
llo
win
g
th
e
eth
ica
l
p
r
in
cip
les
o
u
tlin
ed
in
th
e
H
elsi
n
k
i
Dec
lar
atio
n
.
T
h
e
r
esear
ch
p
r
o
to
c
o
l
was
r
e
v
iewe
d
an
d
a
p
p
r
o
v
ed
b
y
r
e
s
e
a
r
c
h
e
t
h
i
c
s
c
o
m
m
i
t
te
e
o
f
t
h
e
M
o
r
o
c
c
a
n
a
s
s
o
c
ia
t
i
o
n
f
o
r
r
e
s
e
a
r
c
h
a
n
d
e
t
h
i
cs
u
n
d
e
r
t
h
e
i
d
e
n
t
i
f
i
e
r
,
u
n
d
er
ap
p
r
o
v
al
n
u
m
b
er
12
-
R
E
C
-
2022
.
DATA AV
AI
L
AB
I
L
I
T
Y
T
h
e
d
ata
th
at
s
u
p
p
o
r
t
th
e
f
in
d
in
g
s
o
f
th
is
s
tu
d
y
ar
e
av
aila
b
le
o
n
r
eq
u
est
f
r
o
m
th
e
co
r
r
esp
o
n
d
in
g
au
th
o
r
,
[
HE
]
.
T
h
e
d
ata,
w
h
ich
co
n
tain
in
f
o
r
m
atio
n
th
at
co
u
ld
co
m
p
r
o
m
is
e
th
e
p
r
iv
ac
y
o
f
r
esear
ch
p
ar
ticip
an
ts
,
ar
e
n
o
t p
u
b
licly
a
v
ailab
le
d
u
e
to
eth
ical
an
d
p
r
i
v
ac
y
r
estrictio
n
s
.
RE
F
E
R
E
NC
E
S
[
1]
J.
A
.
M
o
r
g
a
d
o
-
D
i
a
z
,
Ed
.
,
G
a
st
ro
i
n
t
e
st
i
n
a
l
c
a
n
c
e
rs
.
Ex
o
n
P
u
b
l
i
c
a
t
i
o
n
s,
2
0
2
2
,
d
o
i
:
1
0
.
3
6
2
5
5
/
e
x
o
n
-
p
u
b
l
i
c
a
t
i
o
n
s
-
g
a
st
r
o
i
n
t
e
st
i
n
a
l
-
c
a
n
c
e
r
s.
[
2
]
J.
S
c
h
w
a
r
t
z
b
a
u
m,
A
.
A
h
l
b
o
m,
a
n
d
M
.
F
e
y
c
h
t
i
n
g
,
“
C
o
h
o
r
t
st
u
d
y
o
f
c
a
n
c
e
r
r
i
sk
a
mo
n
g
mal
e
a
n
d
f
e
mal
e
sh
i
f
t
w
o
r
k
e
r
s,”
S
c
a
n
d
i
n
a
v
i
a
n
J
o
u
rn
a
l
o
f
Wo
rk,
En
v
i
ro
n
m
e
n
t
& H
e
a
l
t
h
,
v
o
l
.
3
3
,
n
o
.
5
,
p
p
.
3
3
6
–
3
4
3
,
O
c
t
.
2
0
0
7
,
d
o
i
:
1
0
.
5
2
7
1
/
sj
w
e
h
.
1
1
5
0
.
[
3
]
G
.
M
a
u
r
i
,
A
.
S
a
r
t
o
r
e
‐
B
i
a
n
c
h
i
,
A
.
R
u
sso
,
S
.
M
a
r
so
n
i
,
A
.
B
a
r
d
e
l
l
i
,
a
n
d
S
.
S
i
e
n
a
,
“
Ea
r
l
y
‐
o
n
set
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
i
n
y
o
u
n
g
i
n
d
i
v
i
d
u
a
l
s,”
Mo
l
e
c
u
l
a
r On
c
o
l
o
g
y
,
v
o
l
.
1
3
,
n
o
.
2
,
p
p
.
1
0
9
–
1
3
1
,
F
e
b
.
2
0
1
9
,
d
o
i
:
1
0
.
1
0
0
2
/
1
8
7
8
-
0
2
6
1
.
1
2
4
1
7
.
[
4
]
V
.
A
.
I
o
n
e
scu
,
G
.
G
h
e
o
r
g
h
e
,
N
.
B
a
c
a
l
b
a
sa,
A
.
L.
C
h
i
o
t
o
r
o
i
u
,
a
n
d
C
.
D
i
a
c
o
n
u
,
“
C
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
:
F
r
o
m
r
i
sk
f
a
c
t
o
r
s
t
o
o
n
c
o
g
e
n
e
si
s,”
Me
d
i
c
i
n
a
,
v
o
l
.
5
9
,
n
o
.
9
,
p
.
1
6
4
6
,
S
e
p
.
2
0
2
3
,
d
o
i
:
1
0
.
3
3
9
0
/
m
e
d
i
c
i
n
a
5
9
0
9
1
6
4
6
.
[
5
]
W
o
r
l
d
C
a
n
c
e
r
R
e
sea
r
c
h
F
u
n
d
/
A
me
r
i
c
a
n
I
n
st
i
t
u
t
e
f
o
r
C
a
n
c
e
r
R
e
sea
r
c
h
,
C
o
n
t
i
n
u
o
u
s
u
p
d
a
t
e
p
ro
j
e
c
t
e
x
p
e
rt
re
p
o
rt
2
0
1
8
:
D
i
e
t
,
n
u
t
ri
t
i
o
n
,
p
h
y
si
c
a
l
a
c
t
i
v
i
t
y
a
n
d
c
o
l
o
rec
t
a
l
c
a
n
c
e
r
.
2
0
1
9
.
[
6
]
K
.
Th
a
n
i
k
a
c
h
a
l
a
m
a
n
d
G
.
K
h
a
n
,
“
C
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
a
n
d
n
u
t
r
i
t
i
o
n
,
”
N
u
t
ri
e
n
t
s
,
v
o
l
.
1
1
,
n
o
.
1
,
p
.
1
6
4
,
Jan
.
2
0
1
9
,
d
o
i
:
1
0
.
3
3
9
0
/
n
u
1
1
0
1
0
1
6
4
.
[
7
]
S
.
T.
O
r
a
n
g
e
,
“
W
h
a
t
i
s
t
h
e
o
p
t
i
mal
t
y
p
e
a
n
d
d
o
se
o
f
p
h
y
si
c
a
l
a
c
t
i
v
i
t
y
f
o
r
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
p
r
e
v
e
n
t
i
o
n
?
,
”
Be
st
Pra
c
t
i
c
e
&
Re
sea
rch
C
l
i
n
i
c
a
l
G
a
st
ro
e
n
t
e
ro
l
o
g
y
,
v
o
l
.
6
6
,
p
.
1
0
1
8
4
1
,
O
c
t
.
2
0
2
3
,
d
o
i
:
1
0
.
1
0
1
6
/
j
.
b
p
g
.
2
0
2
3
.
1
0
1
8
4
1
.
[
8
]
H
.
S
u
n
g
e
t
a
l
.
,
“
G
l
o
b
a
l
c
a
n
c
e
r
st
a
t
i
st
i
c
s
2
0
2
0
:
G
l
o
b
o
c
a
n
e
st
i
mat
e
s
o
f
i
n
c
i
d
e
n
c
e
a
n
d
mo
r
t
a
l
i
t
y
w
o
r
l
d
w
i
d
e
f
o
r
3
6
c
a
n
c
e
r
s
i
n
1
8
5
c
o
u
n
t
r
i
e
s,”
C
A:
A
C
a
n
c
e
r J
o
u
rn
a
l
f
o
r
C
l
i
n
i
c
i
a
n
s
,
v
o
l
.
7
1
,
n
o
.
3
,
p
p
.
2
0
9
–
2
4
9
,
M
a
y
2
0
2
1
,
d
o
i
:
1
0
.
3
3
2
2
/
c
a
a
c
.
2
1
6
6
0
.
[
9
]
C
.
F
i
t
z
mau
r
i
c
e
,
“
G
l
o
b
a
l
,
r
e
g
i
o
n
a
l
,
a
n
d
n
a
t
i
o
n
a
l
c
a
n
c
e
r
i
n
c
i
d
e
n
c
e
,
mo
r
t
a
l
i
t
y
,
y
e
a
r
s
o
f
l
i
f
e
l
o
st
,
y
e
a
r
s
l
i
v
e
d
w
i
t
h
d
i
sab
i
l
i
t
y
,
a
n
d
d
i
sab
i
l
i
t
y
-
a
d
j
u
st
e
d
l
i
f
e
-
y
e
a
r
s
f
o
r
2
9
c
a
n
c
e
r
g
r
o
u
p
s,
2
0
0
6
t
o
2
0
1
6
:
A
sy
st
e
mat
i
c
a
n
a
l
y
si
s
f
o
r
t
h
e
G
l
o
b
a
l
B
u
r
d
e
n
o
f
D
i
sea
se
st
u
d
y
,
”
J
o
u
rn
a
l
o
f
C
l
i
n
i
c
a
l
O
n
c
o
l
o
g
y
,
v
o
l
.
3
6
,
n
o
.
1
5
_
su
p
p
l
,
p
p
.
1
5
6
8
–
1
5
6
8
,
M
a
y
2
0
1
8
,
d
o
i
:
1
0
.
1
2
0
0
/
JC
O
.
2
0
1
8
.
3
6
.
1
5
_
su
p
p
l
.
1
5
6
8
.
[
1
0
]
F
.
A
l
l
a
l
i
,
“
N
u
t
r
i
t
i
o
n
t
r
a
n
si
t
i
o
n
i
n
M
o
r
o
c
c
o
,
”
I
n
t
e
rn
a
t
i
o
n
a
l
J
o
u
rn
a
l
o
f
Me
d
i
c
i
n
e
a
n
d
S
u
rg
e
ry
,
v
o
l
.
4
,
n
o
.
s,
p
p
.
6
8
–
7
1
,
2
0
1
7
,
d
o
i
:
1
0
.
1
5
3
4
2
/
i
j
ms.v
4
i
s.1
4
5
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t J Pu
b
lic
Hea
lth
Sci
I
SS
N:
2252
-
8
8
0
6
R
ela
tio
n
s
h
ip
b
etw
ee
n
s
h
ift w
o
r
k
a
n
d
th
e
r
is
k
o
f c
o
lo
r
ec
ta
l c
a
n
ce
r
a
mo
n
g
M
o
r
o
cc
a
n
…
(
Ha
mza
E
lb
a
ylek
)
1117
[
1
1
]
R
.
S
h
a
r
ma
e
t
a
l
.
,
“
M
a
p
p
i
n
g
c
a
n
c
e
r
i
n
A
f
r
i
c
a
:
A
c
o
mp
r
e
h
e
n
si
v
e
a
n
d
c
o
mp
a
r
a
b
l
e
c
h
a
r
a
c
t
e
r
i
z
a
t
i
o
n
o
f
3
4
c
a
n
c
e
r
t
y
p
e
s
u
si
n
g
e
st
i
mat
e
s
f
r
o
m g
l
o
b
o
c
a
n
2
0
2
0
,
”
Fro
n
t
i
e
rs i
n
Pu
b
l
i
c
H
e
a
l
t
h
,
v
o
l
.
1
0
,
A
p
r
.
2
0
2
2
,
d
o
i
:
1
0
.
3
3
8
9
/
f
p
u
b
h
.
2
0
2
2
.
8
3
9
8
3
5
.
[
1
2
]
F
.
L.
S
a
l
ma,
C
a
n
c
e
r
reg
i
st
ry
o
f
t
h
e
G
ra
n
d
C
a
sa
b
l
a
n
c
a
reg
i
o
n
f
o
r
t
h
e
p
e
ri
o
d
2
0
1
3
-
2017
,
2
0
1
9
.
[
O
n
l
i
n
e
]
.
A
v
a
i
l
a
b
l
e
:
h
t
t
p
s:
/
/
w
w
w
.
c
o
n
t
r
e
l
e
c
a
n
c
e
r
.
ma/
si
t
e
_
med
i
a
/
u
p
l
o
a
d
e
d
_
f
i
l
e
s/
R
e
g
i
st
r
e
_
d
e
s_
C
a
n
c
e
r
s_
d
e
_
l
a
_
R
e
g
i
o
n
_
d
u
_
G
r
a
n
d
_
C
a
sab
l
a
n
c
a
_
2
0
1
3
-
2
0
1
7
.
p
d
f
(
A
c
c
e
ssed
:
Jan
1
1
,
2
0
2
4
)
.
[
1
3
]
M
.
A
.
Ta
z
i
a
n
d
N
.
B
e
n
j
a
a
f
a
r
,
C
a
n
c
e
r
i
n
c
i
d
e
n
c
e
ra
t
e
2
0
0
9
-
2
0
1
2
.
2
0
1
6
.
[
O
n
l
i
n
e
]
.
A
v
a
i
l
a
b
l
e
:
h
t
t
p
s:
/
/
w
w
w
.
i
r
c
.
ma/
i
mag
e
s/
R
e
g
i
st
r
e
_
C
a
n
c
e
r
_
R
a
b
a
t
_
2
0
0
9
-
2
0
1
2
.
p
d
f
.
(
A
c
c
e
ssed
:
Jan
1
1
,
2
0
2
4
)
.
[
1
4
]
T.
C
.
E
r
r
e
n
,
P
.
F
a
l
a
t
u
r
i
,
P
.
M
o
r
f
e
l
d
,
P
.
K
n
a
u
t
h
,
R
.
J
.
R
e
i
t
e
r
,
a
n
d
C
.
P
i
e
k
a
r
sk
i
,
“
S
h
i
f
t
w
o
r
k
a
n
d
c
a
n
c
e
r
,
”
D
e
u
t
sch
e
s
Ärzt
e
b
l
a
t
t
i
n
t
e
rn
a
t
i
o
n
a
l
,
S
e
p
.
2
0
1
0
,
d
o
i
:
1
0
.
3
2
3
8
/
a
r
z
t
e
b
l
.
2
0
1
0
.
0
6
5
7
.
[
1
5
]
C
.
H
e
,
S
.
T.
A
n
a
n
d
,
M
.
H
.
Eb
e
l
l
,
J.
E.
V
e
n
a
,
a
n
d
S
.
W
.
R
o
b
b
,
“
C
i
r
c
a
d
i
a
n
d
i
sr
u
p
t
i
n
g
e
x
p
o
su
r
e
s
a
n
d
b
r
e
a
st
c
a
n
c
e
r
r
i
sk
:
A
met
a
-
a
n
a
l
y
si
s,”
I
n
t
e
rn
a
t
i
o
n
a
l
Arc
h
i
v
e
s
o
f
O
c
c
u
p
a
t
i
o
n
a
l
a
n
d
En
v
i
ro
n
m
e
n
t
a
l
H
e
a
l
t
h
,
v
o
l
.
8
8
,
n
o
.
5
,
p
p
.
5
3
3
–
5
4
7
,
Ju
l
.
2
0
1
5
,
d
o
i
:
1
0
.
1
0
0
7
/
s0
0
4
2
0
-
014
-
0
9
8
6
-
x.
[
1
6
]
K
.
P
a
p
a
n
t
o
n
i
o
u
e
t
a
l
.
,
“
S
h
i
f
t
w
o
r
k
a
n
d
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
r
i
sk
i
n
t
h
e
M
C
C
-
S
p
a
i
n
c
a
se
–
c
o
n
t
r
o
l
st
u
d
y
,
”
S
c
a
n
d
i
n
a
v
i
a
n
J
o
u
rn
a
l
o
f
Wo
rk,
En
v
i
ro
n
m
e
n
t
& H
e
a
l
t
h
,
v
o
l
.
4
3
,
n
o
.
3
,
p
p
.
2
5
0
–
2
5
9
,
M
a
y
2
0
1
7
,
d
o
i
:
1
0
.
5
2
7
1
/
sj
w
e
h
.
3
6
2
6
.
[
1
7
]
W
.
M
.
W
a
l
a
sa
e
t
a
l
.
,
“
A
s
so
c
i
a
t
i
o
n
b
e
t
w
e
e
n
sh
i
f
t
w
o
r
k
a
n
d
t
h
e
r
i
sk
o
f
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
i
n
f
e
mal
e
s:
a
p
o
p
u
l
a
t
i
o
n
-
b
a
sed
c
a
se
–
c
o
n
t
r
o
l
st
u
d
y
,
”
O
c
c
u
p
a
t
i
o
n
a
l
a
n
d
En
v
i
ro
n
m
e
n
t
a
l
Me
d
i
c
i
n
e
,
v
o
l
.
7
5
,
n
o
.
5
,
p
p
.
3
4
4
–
3
5
0
,
M
a
y
2
0
1
8
,
d
o
i
:
1
0
.
1
1
3
6
/
o
e
med
-
2017
-
104657.
[
1
8
]
F
.
E.
I
mad
,
H
.
D
r
i
ssi
,
N
.
Ta
w
f
i
q
,
K
.
B
e
n
d
a
h
h
o
u
,
A
.
B
e
n
i
d
e
r
,
a
n
d
D
.
R
a
d
a
l
l
a
h
,
“
A
c
a
se
-
c
o
n
t
r
o
l
st
u
d
y
o
n
d
i
e
t
a
r
y
r
i
sk
f
a
c
t
o
r
s
f
o
r
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
i
n
M
o
r
o
c
c
o
,
”
Pa
n
Af
ri
c
a
n
Me
d
i
c
a
l
J
o
u
rn
a
l
,
v
o
l
.
3
5
,
F
e
b
.
2
0
2
0
,
d
o
i
:
1
0
.
1
1
6
0
4
/
p
a
mj
.
2
0
2
0
.
3
5
.
5
9
.
1
8
2
1
4
.
[
1
9
]
K
.
El
K
i
n
a
n
y
e
t
a
l
.
,
“
C
o
n
c
o
r
d
a
n
c
e
w
i
t
h
t
h
e
w
o
r
l
d
c
a
n
c
e
r
r
e
sea
r
c
h
F
u
n
d
/
A
me
r
i
c
a
n
i
n
st
i
t
u
t
e
f
o
r
c
a
n
c
e
r
r
e
sea
r
c
h
r
e
c
o
mm
e
n
d
a
t
i
o
n
s
f
o
r
c
a
n
c
e
r
p
r
e
v
e
n
t
i
o
n
a
n
d
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
r
i
sk
i
n
M
o
r
o
c
c
o
:
A
l
a
r
g
e
,
p
o
p
u
l
a
t
i
o
n
‐
b
a
sed
c
a
se
–
c
o
n
t
r
o
l
st
u
d
y
,
”
I
n
t
e
rn
a
t
i
o
n
a
l
J
o
u
rn
a
l
o
f
C
a
n
c
e
r
,
v
o
l
.
1
4
5
,
n
o
.
7
,
p
p
.
1
8
2
9
–
1
8
3
7
,
O
c
t
.
2
0
1
9
,
d
o
i
:
1
0
.
1
0
0
2
/
i
j
c
.
3
2
2
6
3
.
[
2
0
]
E.
A
.
Y
u
a
n
d
D
.
R
.
W
e
a
v
e
r
,
“
D
i
s
r
u
p
t
i
n
g
t
h
e
c
i
r
c
a
d
i
a
n
c
l
o
c
k
:
G
e
n
e
-
sp
e
c
i
f
i
c
e
f
f
e
c
t
s
o
n
a
g
i
n
g
,
c
a
n
c
e
r
,
a
n
d
o
t
h
e
r
p
h
e
n
o
t
y
p
e
s,”
Ag
i
n
g
,
v
o
l
.
3
,
n
o
.
5
,
p
p
.
4
7
9
–
4
9
3
,
M
a
y
2
0
1
1
,
d
o
i
:
1
0
.
1
8
6
3
2
/
a
g
i
n
g
.
1
0
0
3
2
3
.
[
2
1
]
J.
C
h
a
r
a
n
a
n
d
T.
B
i
sw
a
s
,
“
H
o
w
t
o
c
a
l
c
u
l
a
t
e
samp
l
e
si
z
e
f
o
r
d
i
f
f
e
r
e
n
t
st
u
d
y
d
e
si
g
n
s
i
n
med
i
c
a
l
r
e
sea
r
c
h
?
,
”
I
n
d
i
a
n
J
o
u
rn
a
l
o
f
Psy
c
h
o
l
o
g
i
c
a
l
Me
d
i
c
i
n
e
,
v
o
l
.
3
5
,
n
o
.
2
,
p
p
.
1
2
1
–
1
2
6
,
A
p
r
.
2
0
1
3
,
d
o
i
:
1
0
.
4
1
0
3
/
0
2
5
3
-
7
1
7
6
.
1
1
6
2
3
2
.
[
2
2
]
W
o
r
l
d
H
e
a
l
t
h
O
r
g
a
n
i
z
a
t
i
o
n
,
O
b
e
si
t
y
:
Pre
v
e
n
t
i
n
g
a
n
d
m
a
n
a
g
i
n
g
t
h
e
g
l
o
b
a
l
e
p
i
d
e
m
i
c
.
Re
p
o
rt
o
f
a
WHO
c
o
n
su
l
t
a
t
i
o
n
,
v
o
l
.
8
9
4
.
2000.
[
O
n
l
i
n
e
]
.
A
v
a
i
l
a
b
l
e
:
h
t
t
p
s:
/
/
i
r
i
s
.
w
h
o
.
i
n
t
/
h
a
n
d
l
e
/
1
0
6
6
5
/
4
2
3
3
0
.
[
2
3
]
W
o
r
l
d
H
e
a
l
t
h
O
r
g
a
n
i
z
a
t
i
o
n
,
G
l
o
b
a
l
p
h
y
si
c
a
l
a
c
t
i
v
i
t
y
q
u
e
st
i
o
n
n
a
i
re
(
G
PAQ
)
a
n
a
l
y
si
s
g
u
i
d
e
.
S
w
i
t
zerl
a
n
d
:
p
rev
e
n
t
i
o
n
o
f
n
o
n
c
o
m
m
u
n
i
c
a
b
l
e
d
i
sea
ses
d
e
p
a
rt
m
e
n
t
.
su
rve
i
l
l
a
n
c
e
a
n
d
p
o
p
u
l
a
t
i
o
n
-
b
a
sed
p
rev
e
n
t
i
o
n
,
Wo
rl
d
H
e
a
l
t
h
O
rg
a
n
i
za
t
i
o
n
,
2021.
[
2
4
]
K
.
El
K
i
n
a
n
y
e
t
a
l
.
,
“
A
d
a
p
t
a
t
i
o
n
a
n
d
v
a
l
i
d
a
t
i
o
n
o
f
a
f
o
o
d
f
r
e
q
u
e
n
c
y
q
u
e
st
i
o
n
n
a
i
r
e
(
F
F
Q
)
t
o
a
sse
ss
d
i
e
t
a
r
y
i
n
t
a
k
e
i
n
M
o
r
o
c
c
a
n
a
d
u
l
t
s,”
N
u
t
ri
t
i
o
n
J
o
u
rn
a
l
,
v
o
l
.
1
7
,
n
o
.
1
,
p
.
6
1
,
D
e
c
.
2
0
1
8
,
d
o
i
:
1
0
.
1
1
8
6
/
s1
2
9
3
7
-
018
-
0
3
6
8
-
4.
[
2
5
]
M
.
K
h
a
l
i
s
e
t
a
l
.
,
“
U
p
d
a
t
e
o
f
t
h
e
M
o
r
o
c
c
a
n
f
o
o
d
c
o
mp
o
si
t
i
o
n
t
a
b
l
e
s:
To
w
a
r
d
s
a
mo
r
e
r
e
l
i
a
b
l
e
t
o
o
l
f
o
r
n
u
t
r
i
t
i
o
n
r
e
sea
r
c
h
,
”
J
o
u
rn
a
l
o
f
Fo
o
d
C
o
m
p
o
si
t
i
o
n
a
n
d
An
a
l
y
si
s
,
v
o
l
.
8
7
,
p
.
1
0
3
3
9
7
,
A
p
r
.
2
0
2
0
,
d
o
i
:
1
0
.
1
0
1
6
/
j
.
j
f
c
a
.
2
0
1
9
.
1
0
3
3
9
7
.
[
2
6
]
K
.
El
K
i
n
a
n
y
e
t
a
l
.
,
“
C
o
n
su
mp
t
i
o
n
o
f
mo
d
e
r
n
a
n
d
t
r
a
d
i
t
i
o
n
a
l
M
o
r
o
c
c
a
n
d
a
i
r
y
p
r
o
d
u
c
t
s
a
n
d
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
r
i
sk
:
A
l
a
r
g
e
c
a
se
c
o
n
t
r
o
l
st
u
d
y
,
”
Eu
ro
p
e
a
n
J
o
u
rn
a
l
o
f
N
u
t
ri
t
i
o
n
,
v
o
l
.
5
9
,
n
o
.
3
,
p
p
.
9
5
3
–
9
6
3
,
A
p
r
.
2
0
2
0
,
d
o
i
:
1
0
.
1
0
0
7
/
s0
0
3
9
4
-
0
1
9
-
01954
-
1.
[
2
7
]
M
.
S
.
D
e
o
u
l
a
e
t
a
l
.
,
“
C
o
n
su
mp
t
i
o
n
o
f
mea
t
,
t
r
a
d
i
t
i
o
n
a
l
a
n
d
mo
d
e
r
n
p
r
o
c
e
ssed
mea
t
a
n
d
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
r
i
sk
a
mo
n
g
t
h
e
M
o
r
o
c
c
a
n
p
o
p
u
l
a
t
i
o
n
:
A
l
a
r
g
e
‐
sca
l
e
c
a
se
–
c
o
n
t
r
o
l
st
u
d
y
,
”
I
n
t
e
rn
a
t
i
o
n
a
l
J
o
u
rn
a
l
o
f
C
a
n
c
e
r
,
v
o
l
.
1
4
6
,
n
o
.
5
,
p
p
.
1
3
3
3
–
1
3
4
5
,
M
a
r
.
2
0
2
0
,
d
o
i
:
1
0
.
1
0
0
2
/
i
j
c
.
3
2
6
8
9
.
[
2
8
]
L.
Li
e
t
a
l
.
,
“
Ed
u
c
a
t
i
o
n
a
l
l
e
v
e
l
a
n
d
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
r
i
sk
:
t
h
e
med
i
a
t
i
n
g
r
o
l
e
s o
f
l
i
f
e
st
y
l
e
a
n
d
d
i
e
t
a
r
y
f
a
c
t
o
r
s,”
E
u
ro
p
e
a
n
J
o
u
rn
a
l
o
f
C
a
n
c
e
r P
rev
e
n
t
i
o
n
,
v
o
l
.
3
1
,
n
o
.
2
,
p
p
.
1
3
7
–
1
4
4
,
M
a
r
.
2
0
2
2
,
d
o
i
:
1
0
.
1
0
9
7
/
C
EJ.
0
0
0
0
0
0
0
0
0
0
0
0
0
6
9
7
.
[
2
9
]
A
.
D
.
Le
o
,
C
.
M
e
s
sa,
A
.
C
a
v
a
l
l
i
n
i
,
a
n
d
M
.
Li
n
sal
a
t
a
,
“
Est
r
o
g
e
n
s
a
n
d
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
,
”
C
u
rren
t
D
ru
g
T
a
rg
e
t
s
-
I
m
m
u
n
e
,
En
d
o
c
ri
n
e
& M
e
t
a
b
o
l
i
c
D
i
so
rd
e
rs
,
v
o
l
.
1
,
n
o
.
1
,
p
p
.
1
–
1
2
,
M
a
y
2
0
0
1
,
d
o
i
:
1
0
.
2
1
7
4
/
1
5
6
8
0
0
8
0
1
3
3
4
1
7
4
9
.
[
3
0
]
L.
E.
B
a
r
b
e
r
,
T.
V
.
P
h
a
m
,
L.
F
.
W
h
i
t
e
,
H
.
K
.
R
o
y
,
J.
R
.
P
a
l
mer,
a
n
d
K
.
A
.
B
e
r
t
r
a
n
d
,
“
C
i
r
c
a
d
i
a
n
d
i
sr
u
p
t
i
o
n
a
n
d
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
i
n
c
i
d
e
n
c
e
i
n
b
l
a
c
k
w
o
men
,
”
C
a
n
c
e
r
Ep
i
d
e
m
i
o
l
o
g
y
,
Bi
o
m
a
rke
rs
&
Pre
v
e
n
t
i
o
n
,
v
o
l
.
3
2
,
n
o
.
7
,
p
p
.
9
2
7
–
9
3
5
,
Ju
l
.
2
0
2
3
,
d
o
i
:
1
0
.
1
1
5
8
/
1
0
5
5
-
9
9
6
5
.
EP
I
-
22
-
0808.
[
3
1
]
M.
-
E.
P
a
r
e
n
t
,
M
.
El
-
Ze
i
n
,
M
.
-
C
.
R
o
u
ssea
u
,
J.
P
i
n
t
o
s,
a
n
d
J.
S
i
e
mi
a
t
y
c
k
i
,
“
N
i
g
h
t
w
o
r
k
a
n
d
t
h
e
r
i
sk
o
f
c
a
n
c
e
r
a
mo
n
g
men
,
”
Am
e
ri
c
a
n
J
o
u
rn
a
l
o
f
Ep
i
d
e
m
i
o
l
o
g
y
,
v
o
l
.
1
7
6
,
n
o
.
9
,
p
p
.
7
5
1
–
7
5
9
,
N
o
v
.
2
0
1
2
,
d
o
i
:
1
0
.
1
0
9
3
/
a
j
e
/
k
w
s3
1
8
.
[
3
2
]
A
.
D
u
n
e
t
a
l
.
,
“
A
sso
c
i
a
t
i
o
n
b
e
t
w
e
e
n
n
i
g
h
t
-
sh
i
f
t
w
o
r
k
a
n
d
c
a
n
c
e
r
r
i
sk
:
U
p
d
a
t
e
d
sy
st
e
mat
i
c
r
e
v
i
e
w
a
n
d
met
a
-
a
n
a
l
y
si
s,”
Fro
n
t
i
e
rs
i
n
O
n
c
o
l
o
g
y
,
v
o
l
.
1
0
,
Ju
n
.
2
0
2
0
,
d
o
i
:
1
0
.
3
3
8
9
/
f
o
n
c
.
2
0
2
0
.
0
1
0
0
6
.
[
3
3
]
B
.
P
e
p
ł
o
ń
sk
a
e
t
a
l
.
,
“
N
i
g
h
t
sh
i
f
t
w
o
r
k
a
n
d
mo
d
i
f
i
a
b
l
e
l
i
f
e
st
y
l
e
f
a
c
t
o
r
s,”
I
n
t
e
rn
a
t
i
o
n
a
l
J
o
u
rn
a
l
o
f
O
c
c
u
p
a
t
i
o
n
a
l
Me
d
i
c
i
n
e
a
n
d
En
v
i
ro
n
m
e
n
t
a
l
H
e
a
l
t
h
,
v
o
l
.
2
7
,
n
o
.
5
,
p
p
.
6
9
3
–
7
0
6
,
O
c
t
.
2
0
1
4
,
d
o
i
:
1
0
.
2
4
7
8
/
s1
3
3
8
2
-
014
-
0
2
9
8
-
0.
[
3
4
]
Y
.
F
u
j
i
n
o
,
“
O
c
c
u
p
a
t
i
o
n
a
l
f
a
c
t
o
r
s
a
n
d
mo
r
t
a
l
i
t
y
i
n
t
h
e
Jap
a
n
c
o
l
l
a
b
o
r
a
t
i
v
e
c
o
h
o
r
t
st
u
d
y
f
o
r
e
v
a
l
u
a
t
i
o
n
o
f
c
a
n
c
e
r
(
JA
C
C
)
,
”
Asi
a
n
Pa
si
f
i
c
J
o
u
rn
a
l
o
f
C
a
n
c
e
r P
rev
e
n
t
i
o
n
,
v
o
l
.
8
S
u
p
p
l
.
2
0
0
7
.
[
3
5
]
M
.
Y
o
n
g
,
C
.
G
e
r
man
n
,
S
.
La
n
g
,
a
n
d
C
.
O
b
e
r
l
i
n
n
e
r
,
“
P
r
i
ma
r
y
sel
e
c
t
i
o
n
i
n
t
o
sh
i
f
t
w
o
r
k
a
n
d
c
h
a
n
g
e
o
f
c
a
r
d
i
o
v
a
scu
l
a
r
r
i
sk
p
r
o
f
i
l
e
,
”
S
c
a
n
d
i
n
a
v
i
a
n
J
o
u
rn
a
l
o
f
Wo
rk,
En
v
i
ro
n
m
e
n
t
&
H
e
a
l
t
h
,
v
o
l
.
4
1
,
n
o
.
3
,
p
p
.
2
5
9
–
2
6
7
,
M
a
y
2
0
1
5
,
d
o
i
:
1
0
.
5
2
7
1
/
sj
w
e
h
.
3
4
8
7
.
[
3
6
]
G
.
A
t
k
i
n
so
n
a
n
d
D
.
D
a
v
e
n
n
e
,
“
R
e
l
a
t
i
o
n
sh
i
p
s
b
e
t
w
e
e
n
sl
e
e
p
,
p
h
y
si
c
a
l
a
c
t
i
v
i
t
y
a
n
d
h
u
man
h
e
a
l
t
h
,
”
Ph
y
si
o
l
o
g
y
&
Be
h
a
v
i
o
r
,
v
o
l
.
9
0
,
n
o
.
2
–
3
,
p
p
.
2
2
9
–
2
3
5
,
F
e
b
.
2
0
0
7
,
d
o
i
:
1
0
.
1
0
1
6
/
j
.
p
h
y
sb
e
h
.
2
0
0
6
.
0
9
.
0
1
5
.
[
3
7
]
C
.
V
e
t
t
e
r
,
E.
E.
D
e
v
o
r
e
,
C
.
A
.
R
a
mi
n
,
F
.
E.
S
p
e
i
z
e
r
,
W
.
C
.
W
i
l
l
e
t
t
,
a
n
d
E.
S
.
S
c
h
e
r
n
h
a
mm
e
r
,
“
M
i
smat
c
h
o
f
sl
e
e
p
a
n
d
W
o
r
k
t
i
mi
n
g
a
n
d
r
i
sk
o
f
t
y
p
e
2
d
i
a
b
e
t
e
s,”
D
i
a
b
e
t
e
s C
a
re
,
v
o
l
.
3
8
,
n
o
.
9
,
p
p
.
1
7
0
7
–
1
7
1
3
,
S
e
p
.
2
0
1
5
,
d
o
i
:
1
0
.
2
3
3
7
/
d
c
1
5
-
0302.
[
3
8
]
G
.
S
o
l
t
a
n
i
,
A
.
P
o
u
r
sh
e
i
k
h
a
n
i
,
M
.
Y
a
s
si
,
A
.
H
a
y
a
t
b
a
k
h
sh
,
M
.
K
e
r
a
c
h
i
a
n
,
a
n
d
M
.
A
.
K
e
r
a
c
h
i
a
n
,
“
O
b
e
si
t
y
,
d
i
a
b
e
t
e
s
a
n
d
t
h
e
r
i
sk
o
f
c
o
l
o
r
e
c
t
a
l
a
d
e
n
o
ma
a
n
d
c
a
n
c
e
r
,
”
BM
C
En
d
o
c
ri
n
e
D
i
so
rd
e
rs
,
v
o
l
.
1
9
,
n
o
.
1
,
p
.
1
1
3
,
D
e
c
.
2
0
1
9
,
d
o
i
:
1
0
.
1
1
8
6
/
s1
2
9
0
2
-
019
-
0444
-
6.
[
3
9
]
Y
.
S
h
i
e
t
a
l
.
,
“
N
i
g
h
t
-
sh
i
f
t
w
o
r
k
d
u
r
a
t
i
o
n
a
n
d
r
i
sk
o
f
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
a
c
c
o
r
d
i
n
g
t
o
I
R
S
1
a
n
d
I
R
S
2
e
x
p
r
e
ssi
o
n
,
”
C
a
n
c
e
r
Ep
i
d
e
m
i
o
l
o
g
y
,
Bi
o
m
a
rke
rs &
P
rev
e
n
t
i
o
n
,
v
o
l
.
2
9
,
n
o
.
1
,
p
p
.
1
3
3
–
1
4
0
,
Jan
.
2
0
2
0
,
d
o
i
:
1
0
.
1
1
5
8
/
1
0
5
5
-
9
9
6
5
.
EPI
-
19
-
0325.
[
4
0
]
L.
F
u
a
n
d
C
.
C
.
Le
e
,
“
Th
e
c
i
r
c
a
d
i
a
n
c
l
o
c
k
:
p
a
c
e
mak
e
r
a
n
d
t
u
mo
r
su
p
p
r
e
sso
r
,
”
N
a
t
u
re
Re
v
i
e
w
s
C
a
n
c
e
r
,
v
o
l
.
3
,
n
o
.
5
,
p
p
.
3
5
0
–
3
6
1
,
M
a
y
2
0
0
3
,
d
o
i
:
1
0
.
1
0
3
8
/
n
r
c
1
0
7
2
.
[
4
1
]
L.
F
r
i
t
sch
i
e
t
a
l
.
,
“
H
y
p
o
t
h
e
ses
f
o
r
me
c
h
a
n
i
sms
l
i
n
k
i
n
g
sh
i
f
t
w
o
r
k
a
n
d
c
a
n
c
e
r
,
”
Me
d
i
c
a
l
H
y
p
o
t
h
e
ses
,
v
o
l
.
7
7
,
n
o
.
3
,
p
p
.
4
3
0
–
4
3
6
,
S
e
p
.
2
0
1
1
,
d
o
i
:
1
0
.
1
0
1
6
/
j
.
meh
y
.
2
0
1
1
.
0
6
.
0
0
2
.
[
4
2
]
A
.
G
r
u
n
d
y
e
t
a
l
.
,
“
Li
g
h
t
i
n
t
e
n
si
t
y
e
x
p
o
su
r
e
,
sl
e
e
p
d
u
r
a
t
i
o
n
,
p
h
y
si
c
a
l
a
c
t
i
v
i
t
y
,
a
n
d
b
i
o
mark
e
r
s
o
f
mel
a
t
o
n
i
n
a
mo
n
g
r
o
t
a
t
i
n
g
sh
i
f
t
n
u
r
ses,
”
C
h
ro
n
o
b
i
o
l
o
g
y
I
n
t
e
rn
a
t
i
o
n
a
l
,
v
o
l
.
2
6
,
n
o
.
7
,
p
p
.
1
4
4
3
–
1
4
6
1
,
O
c
t
.
2
0
0
9
,
d
o
i
:
1
0
.
3
1
0
9
/
0
7
4
2
0
5
2
0
9
0
3
3
9
9
9
8
7
.
[
4
3
]
S
.
F
o
l
k
a
r
d
,
“
D
o
p
e
r
man
e
n
t
n
i
g
h
t
w
o
r
k
e
r
s
sh
o
w
c
i
r
c
a
d
i
a
n
a
d
j
u
st
men
t
?
A
r
e
v
i
e
w
b
a
sed
o
n
t
h
e
e
n
d
o
g
e
n
o
u
s
mel
a
t
o
n
i
n
r
h
y
t
h
m,”
C
h
ro
n
o
b
i
o
l
o
g
y
I
n
t
e
rn
a
t
i
o
n
a
l
,
v
o
l
.
2
5
,
n
o
.
2
–
3
,
p
p
.
2
1
5
–
2
2
4
,
Jan
.
2
0
0
8
,
d
o
i
:
1
0
.
1
0
8
0
/
0
7
4
2
0
5
2
0
8
0
2
1
0
6
8
3
5
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8
8
0
6
I
n
t J Pu
b
lic
Hea
lth
Sci
,
Vo
l.
14
,
No
.
3
,
Sep
tem
b
er
20
25
:
1
1
0
9
-
1
1
1
8
1118
[
4
4
]
M
.
F
a
r
r
i
o
l
,
Y
.
V
e
n
e
r
e
o
,
X
.
O
r
t
a
,
J.
M
.
C
a
st
e
l
l
a
n
o
s,
a
n
d
T.
S
e
g
o
v
i
a
-
S
i
l
v
e
st
r
e
,
“
I
n
v
i
t
r
o
e
f
f
e
c
t
s
o
f
mel
a
t
o
n
i
n
o
n
c
e
l
l
p
r
o
l
i
f
e
r
a
t
i
o
n
i
n
a
c
o
l
o
n
a
d
e
n
o
c
a
r
c
i
n
o
ma
l
i
n
e
,
”
J
o
u
rn
a
l
o
f
Ap
p
l
i
e
d
T
o
x
i
c
o
l
o
g
y
,
v
o
l
.
2
0
,
n
o
.
1
,
p
p
.
2
1
–
2
4
,
Jan
.
2
0
0
0
,
d
o
i
:
1
0
.
1
0
0
2
/
(
S
I
C
I
)
1
0
9
9
-
1
2
6
3
(
2
0
0
0
0
1
/
0
2
)
2
0
:
1
<
2
1
:
:
A
I
D
-
JA
T
6
2
3
>
3
.
0
.
C
O
;
2
-
M.
[
4
5
]
K
.
P
a
p
a
n
t
o
n
i
o
u
e
t
a
l
.
,
“
R
o
t
a
t
i
n
g
n
i
g
h
t
sh
i
f
t
w
o
r
k
a
n
d
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
r
i
s
k
i
n
t
h
e
n
u
r
ses’
h
e
a
l
t
h
st
u
d
i
e
s,”
I
n
t
e
r
n
a
t
i
o
n
a
l
J
o
u
rn
a
l
o
f
C
a
n
c
e
r
,
v
o
l
.
1
4
3
,
n
o
.
1
1
,
p
p
.
2
7
0
9
–
2
7
1
7
,
D
e
c
.
2
0
1
8
,
d
o
i
:
1
0
.
1
0
0
2
/
i
j
c
.
3
1
6
5
5
.
[
4
6
]
D
.
G
u
e
t
a
l
.
,
“
C
i
r
c
a
d
i
a
n
c
l
o
c
k
p
a
t
h
w
a
y
g
e
n
e
s
a
sso
c
i
a
t
e
d
w
i
t
h
c
o
l
o
r
e
c
t
a
l
c
a
n
c
e
r
r
i
sk
a
n
d
p
r
o
g
n
o
si
s,”
Arc
h
i
v
e
s
o
f
T
o
x
i
c
o
l
o
g
y
,
v
o
l
.
9
2
,
n
o
.
8
,
p
p
.
2
6
8
1
–
2
6
8
9
,
A
u
g
.
2
0
1
8
,
d
o
i
:
1
0
.
1
0
0
7
/
s0
0
2
0
4
-
0
1
8
-
2251
-
7.
[
4
7
]
C
.
S
a
v
v
i
d
i
s
a
n
d
M
.
K
o
u
t
si
l
i
e
r
i
s,
“
C
i
r
c
a
d
i
a
n
r
h
y
t
h
m
d
i
sr
u
p
t
i
o
n
i
n
c
a
n
c
e
r
b
i
o
l
o
g
y
,
”
Mo
l
e
c
u
l
a
r
Me
d
i
c
i
n
e
,
v
o
l
.
1
8
,
n
o
.
9
,
p
p
.
1
2
4
9
–
1
2
6
0
,
S
e
p
.
2
0
1
2
,
d
o
i
:
1
0
.
2
1
1
9
/
mo
l
med
.
2
0
1
2
.
0
0
0
7
7
.
[
4
8
]
E.
E.
D
e
v
o
r
e
e
t
a
l
.
,
“
R
o
t
a
t
i
n
g
n
i
g
h
t
sh
i
f
t
w
o
r
k
,
sl
e
e
p
,
a
n
d
c
o
l
o
r
e
c
t
a
l
a
d
e
n
o
ma
i
n
w
o
men
,
”
I
n
t
e
rn
a
t
i
o
n
a
l
J
o
u
rn
a
l
o
f
C
o
l
o
rec
t
a
l
D
i
sea
se
,
v
o
l
.
3
2
,
n
o
.
7
,
p
p
.
1
0
1
3
–
1
0
1
8
,
Ju
l
.
2
0
1
7
,
d
o
i
:
1
0
.
1
0
0
7
/
s0
0
3
8
4
-
017
-
2758
-
z.
B
I
O
G
RAP
H
I
E
S O
F
AUTH
O
RS
H
a
m
z
a
Elb
a
y
lek
is an
e
p
id
e
m
io
lo
g
ist
a
n
d
p
u
b
l
ic h
e
a
lt
h
re
se
a
rc
h
e
r
sp
e
c
ializin
g
i
n
th
e
stu
d
y
o
f
ris
k
fa
c
to
rs
fo
r
c
o
l
o
re
c
tal
c
a
n
c
e
r
in
M
o
r
o
c
c
o
.
Ba
se
d
a
t
t
h
e
F
a
c
u
l
ty
o
f
S
c
ien
c
e
s
S
e
m
lalia,
Un
iv
e
rsit
y
Ca
d
i
Ay
y
a
d
i
n
M
a
rra
k
e
c
h
,
he
f
o
c
u
se
s
o
n
id
e
n
t
ify
i
n
g
e
n
v
i
ro
n
m
e
n
tal,
g
e
n
e
ti
c
,
a
n
d
l
ifes
ty
le
fa
c
to
rs
c
o
n
tri
b
u
t
in
g
to
t
h
e
d
ise
a
se
.
His
wo
rk
a
ims
to
imp
ro
v
e
c
a
n
c
e
r
p
re
v
e
n
ti
o
n
stra
teg
ies
a
n
d
p
u
b
li
c
h
e
a
lt
h
i
n
terv
e
n
t
io
n
s
b
y
p
r
o
v
i
d
in
g
v
a
l
u
a
b
le
i
n
sig
h
ts
in
t
o
c
o
lo
re
c
tal
c
a
n
c
e
r
e
p
id
e
m
io
lo
g
y
in
th
e
re
g
i
o
n
.
He
c
a
n
b
e
c
o
n
tac
ted
a
t
e
m
a
il
:
h
a
m
z
a
.
e
lb
a
y
lek
@c
e
d
.
u
c
a
.
m
a
.
S
o
u
m
ia
Am
m
o
r
is
a
F
u
l
l
P
ro
fe
ss
o
r
a
t
t
h
e
F
a
c
u
l
ty
o
f
S
c
ien
c
e
s
S
e
m
lalia
,
Un
iv
e
rsity
Ca
d
i
A
y
y
a
d
in
M
a
rra
k
e
c
h
.
He
r
re
se
a
rc
h
fo
c
u
se
s
o
n
th
e
ris
k
fa
c
to
rs
o
f
n
a
so
p
h
a
ry
n
g
e
a
l
c
a
rc
in
o
m
a
,
a
imin
g
t
o
u
n
d
e
rsta
n
d
t
h
e
e
n
v
ir
o
n
m
e
n
tal,
g
e
n
e
ti
c
,
a
n
d
li
fe
sty
le
in
flu
e
n
c
e
s
o
n
th
e
d
ise
a
se
.
Th
ro
u
g
h
h
e
r
wo
r
k
,
t
h
e
y
c
o
n
tri
b
u
te
to
a
d
v
a
n
c
in
g
c
a
n
c
e
r
e
p
id
e
m
io
l
o
g
y
a
n
d
imp
r
o
v
in
g
p
u
b
li
c
h
e
a
lt
h
stra
teg
ies
in
M
o
r
o
c
c
o
.
Sh
e
c
a
n
b
e
c
o
n
tac
ted
a
t
e
m
a
il
:
a
m
m
o
r.
b
e
lk
a
h
ia@
u
c
a
m
.
a
c
.
m
a
.
Evaluation Warning : The document was created with Spire.PDF for Python.