Parental Occupational Exposures and Risk of Childhood Cancer

Abstract

Occupational exposures of parents might be related to cancer in their offspring. Forty-eight published studies on this topic have reported relative risks for over 1000 specific occupation/cancer combinations. Virtually all of the studies employed the case-control design. Occupations and exposures of fathers were investigated much more frequently than those of the mother. Information about parental occupations was derived through interviews or from birth certificates and other administrative records. Specific exposures were typically estimated by industrial hygienists or were self-reported. The studies have several limitations related to the quality of the exposure assessment, small numbers of exposed cases, multiple comparisons, and possible bias toward the reporting of positive results. Despite these limitations, they provide evidence that certain parental exposures may be harmful to children and deserve further study. The strongest evidence is for childhood leukemia and paternal exposure to solvents, paints, and employment in motor vehicle-related occupations; and childhood nervous system cancers and paternal exposure to paints. To more clearly evaluate the importance of these and other exposures in future investigations, we need improvements in four areas: a) more careful attention must be paid to maternal exposures; b) studies should employ more sophisticated exposure assessment techniques; c) careful attention must be paid to the postulated mechanism, timing, and route of exposure; and d) if postnatal exposures are evaluated, studies should provide evidence that the exposure is actually transferred from the workplace to the child's environment.

Full text

Parental
Occupational
Exposures
and
Risk
of
Childhood
Cancer
Joanne
S.
Colt
and
Aaron
Blair
Division
of
Cancer
Epidemiology
and
Genetics,
National
Cancer
Institute,
Rockville,
Maryland
Occupational
exposures
of
parents
might
be
related
to
cancer
in
their
offspring.
Forty-eight
published
studies
on
this
topic
have
reported
relative
risks
for
over
1000
specific
occupation/
cancer
combinations.
Virtually
all
of
the
studies
employed
the
case-control
design.
Occupations
and
exposures
of
fathers
were
investigated
much
more
frequently
than
those
of
the
mother.
Information
about
parental
occupations
was
derived
through
interviews
or
from
birth
certificates
and
other
administrative
records.
Specific
exposures
were
typically
estimated
by
industrial
hygienists
or
were
self-reported.
The
studies
have
several
limitations
related
to
the
quality
of
the
exposure
assessment,
small
numbers
of
exposed
cases,
multiple
comparisons,
and
possible
bias
toward
the
reporting
of
positive
results.
Despite
these
limitations,
they
provide
evidence
that
certain
parental
exposures
may
be
harmful
to
children
and
deserve
further
study.
The
strongest
evidence
is
for
childhood
leukemia
and
paternal
exposure
to
solvents,
paints,
and
employment
in
motor
vehicle-related
occupations;
and
childhood
nervous
system
cancers
and
paternal
exposure
to
paints.
To
more
clearly
evaluate
the
importance
of
these
and
other
exposures
in
future
investigations,
we
need
improvements
in
four
areas:
a)
more
careful
attention
must
be
paid
to
maternal
exposures;
b)
studies
should
employ
more
sophisticated
exposure
assessment
techniques;
c)
careful
attention
must
be
paid
to
the
postulated
mechanism,
timing,
and
route
of
exposure;
and
d)
if
postnatal
exposures
are
evaluated,
studies
should
provide
evidence
that
the
exposure
is
actually
transferred
from
the
workplace
to
the
child's
environment.
Environ
Health
Perspect
1
06(Suppl
3):909-925
(1998).
http://ehpnetl
.niehs.nih.gov/docs/1998/Suppl-3/
909-925coltlabstract.html
Key
words:
children,
cancer,
occupation,
occupational
exposure,
leukemia,
lymphoma,
brain
tumor,
neuroblastoma,
Wilms
tumor
Introduction
The
incidence
of
childhood
cancer
has
been
increasing
nearly
one
percent
per
year
for
the
past
two
decades
(1).
This
increase
is
largely
unexplained,
but
exposure
to
envi-
ronmental
chemicals
is
a
concern.
Because
the
workplace
is
an
important
source
of
environmental
chemicals
and
these
chemi-
cls
may
be
inadvertently
transferred
from
the
workplace
to
the
home,
special
atten-
tion
has
been
paid
to
the
relationship
This
paper
is
based
on
a
presentation
at
the
U.S.
EPA
Conference
on
Preventable
Causes
of
Cancer
in
Children
held
15-16
September
1997
in
Arlington,
Virginia.
Manuscript
received
at
EHP
4
December
1997;
accepted
24
March
1998.
Address
correspondence
to
J.S.
Colt,
National
Cancer
Institute,
6130
Executive
Boulevard,
Room
418,
Rockville,
MD
20892.
Telephone:
(301)
435-4704.
Fax:
(301)
402-1819.
E-mail:
coltjiepndce.nci.nih.gov
Abbreviations
used:
ALL,
acute
lymphocytic
leukemia;
ANLL,
acute
nonlymphocytic
leukemia;
Cl,
confidence
interval;
CNS,
central
nervous
system;
EMF,
electromagnetic
fields;
HCs,
hydrocarbons;
H,
industrial
hygienist;
JEM,
job
exposure
matrix;
NHL,
non-Hodgkin's
lymphoma;
OR,
odds
ratio.
between
parental
occupation
and
the
risk
of
childhood
cancer.
Savitz
and
Chen
(2)
reviewed
the
liter-
ature
on
this
topic
in
1990.
Their
review
covered
24
papers
and
focused
on
the
methodologies
used,
the
findings
for
spe-
cific
occupation/cancer
combinations,
and
the
need
for
further
study.
The
body
of
lit-
erature
has
grown
considerably
since
then,
with
twice
as
many
studies
published
to
date.
This
review
takes
another
look
at
the
relationship
between
cancer
in
children
and
the
occupations
of
their
parents.
Methods
Forty-eight
published
epidemiologic
studies
were
reviewed
for
this
paper,
22
of
which
were
published
subsequent
to
Savitz
and
Chen's
review.
These
studies
provided
relative
risks
for
over
1000
specific
cancer/occupation
or
cancer/exposure
combinations.
To
sort
through
this
welter
of
data,
our
first
step
was
to
create
a
data-
base
tracking
each
relative
risk
and
the
occupation,
industry,
or
exposure
to
which
it
applied,
according
to
the
author.
We
then
combined
occupations
and
exposures
into
categories
to
facilitate
the
analysis.
For
example,
we
created
a
category
called
paints
and
pigments
and
included
findings
that
authors
reported
for
paints
and
pig-
ments,
painting
and
printing
occupations,
and
the
newspaper
and
printing
industry.
The
reader
is
cautioned
that
occupations
grouped
together
because
of
a
common
exposure
may
have
overlapping
exposures
to
other
potentially
carcinogenic
agents.
We
then
developed
a
set
of
criteria
to
identify
the
most
promising
leads
for
eval-
uation
and
further
work.
We
focus
only
on
a)
findings
that
pertained
to
a
specific
childhood
cancer
as
opposed
to
all
cancers
combined,
b)
cancer/occupation/exposure
categories
with
significantly
elevated
rela-
tive
risks
in
two
or
more
studies,
and
c)
relative
risks
based
on
two
or
more
exposed
cases.
For
cancer/occupation/expo-
sure
categories
that
meet
these
criteria,
we
present
all
the
relative
risks
reported,
regardless
of
whether
they
are
excesses
or
deficits.
Along
with
each
relative
risk,
we
also
present
the
number
of
exposed
cases
to
provide
an
indication
of
the
power
of
the
study
to
detect
a
significant
association.
Because
we
are
interested
primarily
in
potentially
hazardous
occupational
expo-
sures,
we
have
chosen
not
to
report
results
for
occupations
in
which
hazardous
expo-
sures
are
unlikely,
such
as
professionals,
sales
workers,
and
clerical
workers.
Savitz
and
Chen
pointed
out
that
some
studies
have
shown
elevated
childhood
cancer
risks
for
these
occupations
and
attributed
this
to
effects
of
high
social
class
rather
than
to
chemical
exposures.
We
have
excluded
findings
related
to
pesticides
because
these
chemicals
are
evaluated
in
another
paper
in
these
proceedings
(3).
Finally,
we
do
not
report
results
for
broadly defined
occu-
pational
groupings
(e.g.,
manufacturing,
service
occupations),
as
they
lack
the
neces-
sary
precision
to
identify
specific
exposures
deserving
future
attention.
Results
Overview
of
the
Studies
Virtually
all
of
the
studies
employed
the
case-control
design.
Exceptions
were
a
proportionate
mortality
study
by
Sanders
et
al.
(4)
and
an
investigation
of
a
possible
cancer
cluster
by
Wilkins
et
al.
(5).
The
majority
of
the
studies
(about
80%)
were
incidence-based
(Table
1).
Although
most
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
R~
lillililmillilililia
....
ilimilownwoom
909

COLT
AND
BLAIR
Table
1.
Overview
of
48
studies
of
childhood
cancer
and
parental
occupations.
Exposure
assessment
Time
frame
Upper
Incidence
Person
Childhood
Reference
methodology
of
exposure
age
limit
or
mortality
exposed
malignancies
covered
Included
in
Savitz
and
Chen
(1990)
(2)
review
Fabia
and
Thuy,
Birth
certificates
1974
(17)
T
IH
assessment
Kantor
et
al.,
Birth
certificate
1979
(46)
+
Fabia
and
Thuy
(17)
classification
Kwa
and
Fine,
Birth
certificate
1980
(20)
+
Fabia
and
Thuy
(17)
classification
Zack
et
al.,
Questionnaire
1980
(41)
+
IH
assessment
Peters
et
al.,
Questionnaire
with
1981
(11)
self-reported
exposures
Hemminki
et
al.,
Occupations
collected
1981
(12)
from
maternal
welfare
centers
Sanders
et
al.,
Child's
death
certificate
1981
(4)
+
IH
assessment
Gold
et
al.,
Questionnaire
+
H
1982(18)
assessment
Prestin-Martin
Questionnaire
et
al.,
1982
(26)
Wilkins
and
Sinks,
Birth
certificate
+
Zack
1984(47)
(41)
classification
Wilkins
and
Sinks,
Birth
certificate
+
JEM
1984
(48)
Hicks
et
al.,
Questionnaire
+
IH
1984
(34)
assessment
Vianna
et
al.,
1984
(33)
Shaw
et
al.,
1984
(54)
Van
Steensel-Moll
et
al.,
1985
(31)
Spitz
and
Johnson,
1985
(6)
Oshan
et
al.,
1986
(55)
lowengart
et
al.,
1987
(28)
Johnson
et
al.,
1987
(13)
Wilkins
and
Koutras,
1988
(7)
Nasca
et
al.,
1988
(21)
Shu
et
al.,
1988
(43)
Buckley
et
al.,
1989
(27)
Bunin
et
al.,
1989
(44)
Questionnaire
+
H
assessment
Birth
certificate
+
H
assessment
Questionnaire
with
self-reported
exposures
+
Zack
(41)
classification
Birth
certificate
+
clustering
scheme
Questionnaire
Questionnaire
with
self-reported
exposure
+
IH
assessment
Birth
certificate
+
HC-related
jobs
according
to
past
studies
Birth
certificate
Questionnaire
+
Zack
(41),
Hicks
(34),
Spitz
(6)
classifications
Questionnaire
with
self-
reported
exposures
Questionnaire
with
self-reported
exposures
+
JEM
Questionnaire
+
JEM
+
clustering
scheme
At
birth
4
Mortality
At
birth
19
14
At
birth
Year
before
birth,
at
birth,
after
birth
Preconception
through
postnatal
During
pregnancy
At
child's
death
Before
birth,
after
birth
During
pregnancy
At
birth
At
birth
Year
before
birth
Before
birth
At
birth
During
pregnancy,
after
birth
At
birth
Before
birth,
after
birth
Preconception,
during
pregnancy,
after
birth
At
birth
At
birth
At
birth,
at
diagnosis
Preconception,
during
pregnancy
Lifetime
Preconception,
during
pregnancy,
after
birth
Incidence
Mortality
15
Incidence
9
14
14
19
24
NA
NA
15
15
14
14
15
10
Incidence
Incidence
Mortality
Incidence
Incidence
Incidence
Incidence
Incidence
Incidence
Incidence
Incidence
Mortality
Incidence
Incidence
Father
Father
Father
Father
Father,
mother
Father,
mother
Father
Father,
mother
Mother
Father
Father
Father,
mother
Father
Father
Father,
mother
Father
Father
Father
14
Mortality
Father
19
14
15
18
Mortality
Incidence
Incidence
Incidence
14
Incidence
Father
Father,
mother
Father,
mother
Father,
mother
Father,
mother
Total
cancer,
leukemia
+
lymphoma,
nervous
system,
Wilms
Wilms
Total
cancer,
leukemia
+
lymphoma,
nervous
system,
urinary
system
Total
cancer,
leukemia
+
lymphoma,
nervous
system,
Wilms
Brain
Total
cancer,
leukemia,
brain
Total
cancer,
leukemia,
brain,
kidney
Leukemia,
brain
Brain
Wilms
Wilms
Total
cancer,
leukemia
+
lymphoma,
nervous
system,
Wilms,
bone,
rhabdomyosarcoma,
retinoblastoma
Acute
leukemia
Leukemia
ALL
Neuroblastoma
Brain
Acute
leukemia
Intracranial
and
spinal
cord
Brain
Nervous
system
Leukemia
ANLL
Wilms
(Continued)
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
910

PARENTAL
OCCUPATION
AND
CHILDHOOD
CANCER
Table
1.
Continued.
Exposure
assessment
Time
frame
Upper
Incidence
Person
Childhood
Reference
methodology
of
exposure
age
limit
or
mortality
exposed
malignancies
covered
Not
included
in
Savitz
and
Chen
(1990)
(2)
review
Hakulinen
et
al.,
Occupation
reported
to
1976
(19)
maternity
welfare
district
+
Fabia
and
Thuy
(17)
classification
Gold
et
al.,
Questionnaire
with
self-
1979
(56)
reported
exposures
Howe
et
al.,
1989
(24)
Questionnaire
Johnson
and
Spitz,
Birth
certificate
+
Spitz
(6)
1989
(8)
classification
Wilkins
and
Sinks,
Questionnaire
+
JEM
+
1990
(16)
clustering
scheme
Bunin
et
al.,
Questionnaire
+
Spitz
(6)
1990
(57)
classification
Bunin
et
al.,
Questionnaire
+
JEM
+
1990
(58)
clustering
scheme
Wilkins
and
Hundley,
Questionnaire
+
JEM
+
1990
(25)
clustering
scheme
Gardner
et
al.,
Birth
certificate,
1990
(35)
questionnaire
+
industry
dosimetry
records
Magnani
et
al.,
Questionnaire
1990
(32)
Olsen
et
al.,
Pension
fund
files
1991
(23)
Infante-Rivard
et
al.,
1991
(42)
Wilkins
et
al.,
1991
(5)
McKinney
et
al.,
1991
(29)
Urquhart
et
al.,
1991
(37)
Kuijten
et
al.,
1992
(9)
Feingold
et
al.,
1992
(22)
Sorahan
et
al.,
1993
(40)
McLaughlin
et
al.,
1993
(39)
Roman
et
al.,
1993
(36)
Kinlen
et
al.,
1993
(38)
Sorahan
et
al.,
1995
(59)
Wilkins
and
Wellage,
1996
(60)
Gelberg
et
al.,
1997
(61)
Questionnaire
with
self-
reported
exposures
+
IH
assessment
Questionnaire
Questionnaire
with
self-
reported
exposures
Questionnaire
+
occupational
records
on
radiation
dose
Questionnaire
+
Hicks
(34)
and
Vianna
(33)
classifications
Questionnaire
+
JEM
Questionnaire
+
IH
assessment
Linkage
with
National
Dose
Registry
Questionnaire
+
linkage
to
nuclear
industry
database
Scottish
nuclear
industry
and
National
Radiological
Protection
Board
Questionnaire
+
IH
assessment
Questionnaire
+
classification
scheme
Questionnaire
During
pregnancy
14
Before
birth,
19
after
birth
Before
birth
19
Atbirth
14
Preconception,
19
during
pregnancy,
after
birth
Preconception,
during
NA
pregnancy
Preconception,
NA
postconception
At
birth
15
Preconception,
24
at
birth
Before
birth,
NA
after
birth
At
time
of
conception,
20
most
recent
During
pregnancy
14
Preconception,during
19
pregnancy,
after
birth
Preconception,
during
14
pregnancy,
after
birth
Preconception
14
Preconception,
during
14
pregnancy,
after
birth
Year
prior
to
birth
14
Preconception
1
5
Preconception
14
Preconception,
during
4
pregnancy,
after
birth
Preconception
24
Preconception,
1
5
postconception
Preconception,
during
19
pregnancy
During
pregnancy,
24
after
birth
Incidence
Incidence
Incidence
Mortality
Incidence
Incidence
Incidence
Incidence
Incidence
Incidence
Incidence
Father
Father,
mother
Father,
mother
Father
Father,
mother
Father,
mother
Father,
mother
Father
Father
Father,
mother
Father,
mother
Incidence
Mother
Incidence
Incidence
Incidence
Father,
mother
Father,
mother
Father
Total
cancer,
leukemia
+
lymphoma,
brain
Brain
Brain
Nervous
system
Brain
Neuroblastoma
Retinoblastoma
Neuroblastoma
Leukemia,
leukemia
+
NHL
ALL,
ANLL,
NHL
Total
cancer,
leukemia
+
lymphoma,
central
nervous
system,
sympathetic
nervous
system,
renal,
bone,
retinoblastoma,
hepatic,
sarcoma,
germ
cell
ALL
Intracranial
tumors
Leukemia
+
NHL
Leukemia
+
NHL
Incidence
Father,
mother
Brain
(astrocytoma)
Incidence
Mortality
Incidence
Incidence
Incidence
Mortality
Incidence
Incidence
Father,
mother
Father
Father
Father,
mother
Father
Father
Father
Father,
mother
Total
cancer,
ALL,
brain
Total
cancer,
leukemia,
leukemia
+
lymphoma
Leukemia
Leukemia
+
NHL
Leukemia,
leukemia
+NHL
Total
cancer
Nervous
system
Osteosarcoma
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
Abbreviations:
IH,
industrial
hygienist;
JEM,
job
exposure
matrix;
NA,
not
available
from
published
report;
NHL,
Non-Hodgkin
lymphoma.
911

COLT
AND
BLWAR
studies
limited
the
maximum
age
of
cases
to
the
teen
years,
four
were
restricted
to
children
under
10
years
of
age
and
five
investigations
included
young
adults
20
years
of
age
or
older
(the
maximum
age
is
24
years).
The
number
of
investigations
varied
by
tumor.
Cancers
of
the
nervous
system
(26
studies)
and
leukemia/lym-
phomas
(25
studies)
have
received
the
most
attention.
Ten
studies
examined
urinary
system
cancers,
only
one
of
which
was
published
after
Savitz
and
Chen's
review,
and
bone
cancer
and
retinoblastoma
were
each
addressed
in
three
studies.
Occupations
and
exposures
of
fathers
have
been
investigated
much
more
fre-
quently
than
those
of
the
mother.
Forty-
six
of
the
48
studies
examined
paternal
occupations
or
exposures,
but
only
about
half
of
the
studies
addressed
maternal
occupations
or
exposures.
This
is
some-
what
surprising
as
maternal
exposures
are
clearly
more
important
for
fetal
exposure
than
paternal.
Maternal
occupations
have
received
somewhat
more
attention
in
the
more
recent
studies.
Several
methods
were
used
to
obtain
occupational
information,
and
the
way
this
information
was
used
in
analyses
varied.
Thirty-one
studies
obtained
information
about
parents'
occupations
from
question-
naires
administered
to
one
or
both
parents,
11
used
the
parental
occupation
listed
on
the
child's
birth
certificate,
and
6
studies
used
other
records
such
as
the
child's
death
certificate,
maternal
health
records,
or
pen-
sion
fund
files.
About
one-fifth
of
the
studies
presented
cancer
risks
only
for
job
titles,
whereas
the
majority
of
the
studies
calculated
odds
ratios
for
specific
exposures
as
well
as
job
titles.
In
studies
evaluating
specific
chemicals,
exposures
were
typically
based
on
estimates
by
industrial
hygienists
(IH)
or
from
established
job
exposure
matri-
ces.
In
7
studies,
occupational
exposures
were
self-reported.
Although
the
timing
of
exposure
is
rele-
vant
to
the
mechanism
of
action,
it
was
not
always
clearly
indicated
in
the
reports.
Risk
of
childhood
cancer
could
occur
from
damage
to
germ
cells
(for
exposures
that
occur
prior
to
conception)
or
from
direct
effects
on
the
individual
(transplacental
or
postnatal
exposure).
Some
studies
reported
results
for
two
or
more
time
periods
(e.g.,
before
and
after
conception,
before
and
after
birth),
and
a
few
reported
results
for
three
periods
(preconception,
during
preg-
nancy,
and
after
birth).
Overall,
the
pre-
conception,
pregnancy,
and
postnatal
periods
have
received
about
equal
attention
in
the
literature,
with
the
preconception
period
receiving
increased
attention
in
the
more
recent
studies.
Nervous
System
Cancers
Of
the
26
studies
that
looked
at
nervous
system
cancers,
over
half
focused
on
brain
tumors.
Three
studies
focused
exclusively
on
neuroblastoma,
a
malignancy
whose
etiol-
ogy
could
be
different
from
those
of
the
other
nervous
system
cancers.
Paternal
expo-
sures
with
significant
associations
with
childhood
nervous
system
cancers
in
multi-
ple
studies
include
electromagnetic
fields
(EMF),
paints
and
pigments,
hydrocarbons
(HCs),
metals,
and
paternal
employment
in
motor
vehicle-related
occupations
(Table
2).
The
first
three
of
these
categories
were
also
identified
by
Savitz
and
Chen
as
exposures
that
warrant
further
study.
In
1985,
Spitz
and
Johnson
(6)
reported
a
significant
increase
in
neuro-
blastoma
deaths
among
children
whose
fathers
had
worked
in
a
group
of
occupa-
tions
classified
as
having
EMF
exposure.
Several
significant
associations
between
var-
ious
cancers
of
the
nervous
system
and
indi-
vidual
occupations
believed
to
involve
EMF
exposure
have
been
reported
since
then,
including
work
in
electrical
assembly/instal-
lation/repair
occupations
(7);
electricians,
construction
electricians,
and
workers
in
electronics
manufacturing
industries
(8);
employment
at
a
electronic
components
manufacturing
plant
(5);
and
electrical
repair
workers
(9).
A
number
of
other
non-
significant
associations
with
possible
EMF-
related
jobs
have
been
reported.
Brain
cancer
among
adults
has
been
associated
with
employment
in
electricity-related
occupations
in
a
number
of
studies
(10).
Paternal
exposure
to
paints
and/or
inks
has
been
implicated
as
a
risk
factor
for
childhood
cancers
of
the
nervous
system
in
most
investigations
that
have
evaluated
this
issue
(9,11-13).
Many
relative
risks
were
statistically
significant
and
several
were
quite
large
(i.e.,
5.0
or
larger).
Brain
cancer
in
adults
has
been
associated
with
solvent-
related
occupations
(14),
and
many
sol-
vents
have
nonneoplastic
neurobehavioral
effects
(15).
It
is
interesting
to
note
that
in
the
study
by
Wilkins
and
Sinks
(16),
brain
cancer
risk
was
elevated
among
children
of
fathers
occupationally
exposed
to
certain
aromatic
amines
that
have
been
used
in
some
dyes
and
pigments.
In
the
earliest
study
of
parental
occupa-
tion
and
childhood
cancer,
Fabia
and
Thuy
(17)
noted
a
significant
3-fold
increase
in
deaths
from
nervous
system
cancers
from
parental
occupational
contact
with
HCs.
Many
others
have
presented
results
on
this
exposure,
with
significant
excesses
observed
in
two
studies
(6,18).
However,
the
finding
by
Gold
et
al.
(18)
was
not
consistent
for
different
control
groups
and
the
authors
concluded
that
the
study
did
not
support
such
an
association.
For
six
other
studies
(4,13,19-22),
the
relative
risks
for
nervous
system
cancer
and
parental
occupations
with
potential
hydrocarbon
exposure
were
unimpressive.
Many
of
the
relative
risks
were
less
than
1.0,
and
those
that
exceeded
1.0
did
so
only
slightly
and
the
differences
were
not
significant.
Exposures
in
this
grouping
of
occupations
are
quite
varied
in
terms
of
the
specific
chemicals
and
levels
involved;
thus
an
inconsistent
pattern
of
risk
is
not
surprising.
Paternal
occupations
and
industries
associated
with
metals
were
found
to
be
significantly
associated
with
brain
cancer
in
two
studies (7,16),
but
studies
by
Kuijten
et
al.
(9)
and
Feingold
et
al.
(22)
showed
little
evidence
for
such
an
association.
Metals
generally
have
not
been
associated
with
the
development
of
brain
cancers
in
adults
or
in
experimental
animals
(10).
Paternal
employment
in
motor
vehicle-
related
occupations
was
significantly
associ-
ated
with
childhood
nervous
system
cancers
in
two
studies
(17,23),
and
two
other
studies
had
elevated
relative
risks
but
small
numbers
of
exposed
cases
(16,24).
However,
most
studies
that
have
examined
these
types
of
occupations
have
not
found
an
association
(7,9,12,13,18-20,25),
with
relative
risks
typically
less
than
1.0.
Adult
brain
cancer
generally
has
not
been
found
to
be
excessive
among
various
motor
vehicle
drivers
(10).
Four
other
paternal
occupations/
exposures
were
named
as
promising
leads
for
further
study
of
childhood
nervous
sys-
tem
cancers
by
Savitz
and
Chen:
the
pulp
and
paper
industry,
the
chemical
industry,
the
petroleum
industry,
and
ionizing
radi-
ation.
The
pulp
and
paper
industry
was
examined
in
three
studies
subsequent
to
Savitz
and
Chen's
review,
with
odds
ratios
(ORs)
ranging
from
0.8
to
5.0,
none
of
them
statistically
significant;
the
preva-
lence
of
exposure
was
low
(9,16,25).
Two
recent
studies
of
the
chemical
industry
found
elevated
ORs
(9,23),
one
of
them
significant
(23).
No
association
was
found
in
a
study
that
combined
chemical
and
petroleum
refinery
workers
(9).
Only
one
study
of
ionizing
radiation
has
been
per-
formed
since
1990
(9),
and
no
association
was
found.
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
912

PARENTAL
OCCUPATION
AND
CHILDHOOD
CANCER
Table
2.
Childhood
nervous
system
cancers
and
paternal
occupations
with
significant
findings
in
multiple
studies.
Number
of
Relative
exposed
Reference
Histology
Industry
or
occupation
Exposure
Time
frame
risk
95%
Cl
cases
Comments
Electromagnetic
fields
Spitz
and
Johnson,
Neuro-
Electricians, electric
and
1985
(6)
blastoma
electronic
workers,
linemen,
welders,
utility
employees
Electricians,
electric
and
electronic
workers,
linemen,
welders,
utility
employees,
electrical
equipment
salesmen
and
repairmen
Electronics
workers
only
Wilkins
and
Koutras,
Brain
1988
(7)
Nasca
et
al.,
Nervo
1988
(21)
syste
Structural
work:
electrical
assembling,
installation,
and
repair
occupations
Machinery
industry:
electrical
assembly,
installation,
repair
occupations
Bench
occupations:
assembly
and
repair
of
electrical
equipment
us
Electricians,
electronics
workers,
em
power
linemen
Electricians,
electronics
workers,
power
linemen,
electric
equipment
repairmen,
utility
workers
Johnson
and
Spitz,
Central
Industries
1989
(8)
nervous
Electronics
manufacturing
system
Computer
and
office
machine
manufacturing
Refrigeration
and
air
conditioning
manufacturing
Electrical
and
electronic
apparatus
manufacturing
Elecronic
components
manufacturing
Telephone
communications
Electric
utilities
Electric
repair
Occupations
Radio
operators
Electrical
goods
and
applicance
salesmen
Computer
and
business
machine,
power
plant,
utilities
service
mechanics
Electrical
and
electronics
assemblers
and
mechanics
Electronics
assemblers
and
mechanics
Electrical
and
electronics
assemblers,
installers,
mechanics
Electricians
Construction
electricians
Bunin
et
al.,
Neuro-
Electricians;
electrical
and
1990
(57)
blastoma
electronics
workers;
linemen,
welders,
utility
employees
Electricians;
electrical
and
electronics
workers;
linemen,
welders,
utility
employees;
electrical
equipment
salesmen
and
repairmen
Electrical
and
electronic
products
workers
Electrical
and
electronic
products
assemblers
EMF
At
birth
EMF
2.14
0.95-4.8
13
2.13
1.05-4.4
17
EMF
At
birth
EMF
EMF
EMF
EMF
EMF
EMF
EMF
EMF
EMF
EMF
EMF
EMF
EMF
EMF
EMF
At
birth
At
diagnosis
At
birth
At
diagnosis
At
birth
EMF
EMF
EMF
11.75
1.4-98.6
6
2.70
1.2-6.1
19
3.60
1.3-10.0
16
1.00
0.3-3.7
4
1.70
1.28
1.61
1.14
1.64
3.56
4.07
1.36
1.42
3.05
1.22
2.71
1.63
1.44
2.01
1.01
2.68
2.01
3.01
1.34
EMF
3.52
EMF
10.05
EMF
Preconception
1.30
During
pregnancy
0.30
EMF
Preconception
1.00
During
pregnancy
0.60
EMF
EMF
Preconception
1.60
During
pregnancy
0.40
Preconception
4.00
0.8-3.6
1
5
0.6-2.9
1
1
0.8-3.1
19
0.5-2.5
12
0.96-2.8
25
1.04-12.2
7
0.7-22.3
4
0.2-8.2
2
0.5-3.8
7
0.5-18.3
3
0.3-5.1
3
0.6-1
2.2
4
0.4-6.1
4
0.9-2.4
28
0.3-14.3
2
0.2-5.5
2
0.6-1
2.0
4
0.5-8.1
4
0.5-18.1
3
0.6-3.0
10
1.02-12.1
7
1.2-86.3
5
0.4-4.1
16a
0.1-1.3
12a
0.4-2.3
28a
0.2-1.6
lga
0.5-6.2
13a
0.1-1.6
lla
0.4-195
5a
(Continued
on
next
page)
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
913

COLT
AND
BLAIR
Table
2.
Continued.
Number
of
Relative
exposed
Reference
Histology
Industry
or
occupation
Exposure
Time
frame
risk
95%
Cl
cases
Comments
Wilkins
and
Hundley,
Neuro-
Different
clustering
EMF
At
birth
0.5-1.9
NS
4-24
1990
(25)
blastoma
Wilkins
et
al.,
Brain
1991
(5)
schemes
Electronic
components
manufacturer
Brain
Electrical
assembling,
(astrocytoma)
installing,
repair
Electrical
repair
only
Wilkins
and
Wellage,
Brain
1996
(60)
Welding-related
employment
Welding
73.30
26.5-157.5
6
Standardized
incidence
ratio
for
possible
cancer
cluster
Preconception
1.00
0.4-2.8
18a
During
pregnancy
1.00
0.3-3.7
12a
After
birth
1.00
0.3-3.7
12a
Preconception
8.00
1.1-356
ga
During
pregnancy
5.00
0.6-237
6a
After
birth
2.50
0.4-26.2
7a
EMF
Preconception
1.10
0.4-3.1
1
ga
(definite)
During
pregnancy
0.90
0.3-2.6
17a
After
birth
0.80
0.2-2.3
16a
EMF
Preconception
1.70
0.7-4.4
27a
(probable)
During
pregnancy
1.60
0.6-4.5
21a
After
birth
1.30
0.5-3.6
21a
EMF
Preconception
1.31
0.6-3.0
11
During
pregnancy
1.03
0.5-2.4
9
EMF
Preconception
3.83
0.95-15.6
6
During
pregnancy
2.50
0.7-9.3
5
EMF
Preconception
1.75
0.2-13.2
3
During
pregnancy
1.00
0.1-11.0
2
Paints
and
pigments
Kwa
and
Fine,
1980
(20)
Peters
et
al.,
1981
(11)
Hemminki
et
al.,
1981
(12)
Johnson
et
al.,
1987
(13)
Kuijten
et
al.,
1992
(9)
Hydrocarbons
Fabia
and
Thuy,
1974
(17)
Hakulinen
et
al.,
1976
(19)
Nervous
system
Brain
Brain
Printers
At
birth
NA
Paints
Year
before
7.00
pregnancy
through
diagnosis
During
pregnancy
2.59
5.00
Painter
Nervous
Painters
HCs
system
Printing
workers
HCs
Graphic
arts
workers
HCs
Newspaper
and
HCs
printing
industries
Brain
Newspaper
and
(astrocytoma)
printing
industry
Printing
workers
Paint
Nervous
Motor
vehicle
mechanic,
HCs
system
service
station
attendant
Machinist,
miner,
HCs
lumberman
Brain
Motor
vehicle
drivers
HCs
Motor
vehicle
mechanics,
HCs
machinists,
miners,
painters,
dyers,
printers
Motor
vehicle
mechanics,
HCs
machinists,
miners,
painter,
dyers,
printers,
motor
vehicle
drivers
At
birth
NS
2
S
7
NS
14a
Results
for
entire
study
S
period
7a
Results
for
1969-1975
only
1.00
0.3-3.3
4.50
1.4-14.7
9
21.90
1.2-397
5
5.10
1.6-16.3
10
Preconception
1.50
0.4-7.2
1oa
During
pregnancy
1.30
0.7-6.3
ga
After
birth
1.20
0.3-4.2
13a
Preconception
4.00
0.4-195
5a
During
pregnancy
3.00
0.2-157
4a
After
birth
2.50
0.4-26.2
7a
t
After
birth
Infinity
0.7-infinity
4a
At
birth
[2.82]
[0.42]
S
NS
10
2
During
pregnancy
0.67
0.3-1.5
[16]
1.40
0.5-3.9
[11]
0.88
0.5-1.7
[271
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
Kuijten
et
al.,
1992
(9)
(Continued)
914

PARENTAL
OCCUPATION
AND
CHILDHOOD
CANCER
Table
2.
Continued.
Number
of
Relative
exposed
Reference
Histology
Industry
or
occupation
Exposure
Time
frame
Risk
95%
Cl
cases
Comments
Kwa
and
Fine,
Nervous
Mechanics,
service
HCs
At
birth
1.00
NS
6
ORs
were
Spitz
and
Johnson,
Neuro-
1985
(6)
blastoma
system
station
attendants
Machinists
Miners,
engineering
and
allied
trades,
textiles,
printing
press
operators,
painters
and
decorators,
dry
cleaners,
motor
vehicle
drivers
HCs
HCs
Factory
workers,
machinists,
HCs
drivers,
motor
vehicle
mechanics,
service
station
attendants,
lumbermen,
HCs
painters,
dyers,
HCs
cleaners
HCs
Aromatic
and
aliph-
atic
HCs
HCs
Aircraft
industry
workers
HCs
Machine
repairmen
HCs
Paper
and
pulp
HCs
mill
workers
Factory
workers,
HCs
machinists,
steelworkers
Motor
vehicle
mechanics,
HCs
machinists,
miners,
painters,
dyers,
printers
Motor
vehicle
mechanics,
HCs
service
station
attendants
Narrow
definition
HCs
Broad
definition
HCs
HCs
Aromatic
HCs
Alicyclic
HCs
Alkylating
agents
Aliphatic
HCs
At
child's
death
Before
birth
After
birth
At
birth
At
birth
calculated
by
Savitz
and
Chen
(1990)
(2)
0.70
NS
9
0.91
NS
260
0.54-2.3
NS
10-20a
Results
are
for
two
control
groups
0.85
NS
24a
Healthy
controls
4.00
S
158
Cancer
controls
NA
NS
NA
3.17
1.1-8.9
10
0.7-1.1
NS
NA
Results
are
for
different
groups
of
HC-related
jobs
1.00
1.50
4.00
1.20
1.00
0.5-2.3
NA
0.8-2.7
NA
0.4-43.7
NA
0.9-1.6
NA
0.7-1.6
NA
0.70
0.3-1.5
NA
At
birth
At
diagnosis
At
birth
At
diagnosis
During
pregnancy
1.25
1.11
1.41
1.22
0.80
1.10
0.80
1.30
0.7-2.4
18
0.5-2.3
13
0.9-2.2
38
0.7-2.0
29
0.3-2.0
18
0.4-3.0
18
0.2-4.4
4
0.4-4.0
9
0.80
0.3-2.2
15
At
birth
Metal
industry
Metal
related
occupations
Metal
industry:
processing
occupations
Metal
industry:
machine
trades
occupations
Metal
industry:
structural
work
occupations
Machine
trades
occupations:
metal
machining
occupations
1.80
1.60
5.30
1.40
3.90
1.
10
1.1-2.9
62
1.1-2.3
93
1.0-27.2
9
0.6-3.2
17
1.2-12.8
12
0.6-1.8
30
(Continued
on
next
page)
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
1980
(20)
Sanders
at
al.,
1981
(4)
Gold
et
al.,
1982(18)
Brain
Brain
Johnson
et
al.,
1987
(13)
Nasca
et
al.,
1988
(21)
Feingold
et
al.,
1992
(22)
Metals
Wilkins
and
Koutras,
1988
(7)
Nervous
system
CNS
Brain
Brain
915

COLT
AND
BLAIR
Table
2.
Continued.
Number
of
Relative
exposed
Reference
Histology
Industry
or
occupation
Exposure
Time
frame
risk
95%
Cl
cases
Comments
Wilkins
and
Koutras,
Brain
Machine
trades
occupations:
1.60
0.7-3.7
14
Wilkins
and
Sinks,
Brain
1990
(16)
Kuijten
et
al.,
Brain
1992
(9)
(astro-
cytoma)
Feingold
et
al.,
Brain
1992
(22)
Motor
vehicle-related
occupations
Fabia
and
Thuy,
Nervous
1974
(17)
system
Hakulinen
et
al.,
Brain
1976
(19)
Kwa
and
Fine,
Nervous
1980
(20)
system
metalworking
occupations
Processing
occupations:
occupations
in
processing
of
metal
Bench
occupations:
fabrication,
assembly,
repair
of
metal
products
Structural
work:
occupations
in
metal
fabricating
Metal
industry
Metal-related
occupations
Inorganics
(metals
and
metalloids)
Motor
vehicle
mechanic,
service
station
attendant
Motor
vehicle
drivers
HCs
HCs
Motor
vehicle
driver
Mechanics,
gas
station
attendants
Motor
vehicle
driver
Driver,
mechanic,
service
station
attendant,
railroad
worker/engineer
Driver
5.00
0.6-46.1
4
1.40
0.6-3.4
12
2.60
0.8-8.7
1
0
Preconception
3.30
During
pregnancy
2.00
After
birth
1.70
Preconception
1.10
During
pregnancy
0.90
After
birth
0.80
During
pregnancy
1.20
At
birth
During
pregnancy
After
birth
At
birth
HCs
During
pregnancy
Before
birth
After
birth
[2.82]
0.67
1.3-8.5
13
0.8-5.1
10
0.7-3.7
16
0.5-2.1
41a
0.4-2.0
32a
0.4-1.8
33a
0.4-3.3
17
Odds
ratios
for
individual
metals
were
not
significant
S
10
0.3-1.5
[16]
0.60
NS
5
ORs
calculated
by
Savitz
and
Chen
(1990)
(2)
1.00
NS
6
0.92
NS
84a
0.33-0.50
NS
6-12a
Results
are
for
two
control
groups
0.67-1.00
NS
10-1
5a
Nervous
Motor
vehicle
mechanics,
HCs
system
service
station
attendants
Wilkins
and
Koutras,
Brain
1988
(7)
Howe
et
al.,
Brain
1989
(24)
Wilkins
and
Sinks,
Brain
1990(16)
Wilkins
and
Hundley,
Neuro-
1990
(25)
blastoma
Transportation
industry
Transportation
industry:
machine
trades
occupations
Transportation
industry:
motor
freight
and
transportation
occupations
Motor
freight
and
transportation
occupations
Drivers
Mechanics
Motor
freight
and
transportation
Transportation
industry
Transportation
industry:
motor
freight
and
transportation
At
birth
At
birth
Before
birth
Preconcepti.on
During
pregnancy
After
birth
Preconception
During
pregnancy
After
birth
At
birth
0.70
0.3-1.5
NA
1.60
1.0-2.4
97
1.00
0.5-2.1
18
1.60
0.9-3.1
37
1.60
0.9-2.7
26
3.70
0.7-20.7
5
0.96
0.2-4.7
4
2.30
0.7-8.1
6
1.80
0.6-5.4
7
1.70
0.7-4.5
9
1.30
0.6-3.2
13
1.70
0.7-3.9
1
5
1.20
0.8-1.8
22
0.80
0.4-1.5
18
0.80
0.3-1.9
7
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
1988
(7)
Hemminki
et
al.,
1981
(12)
Gold
et
al.,
1982(18)
Brain
Brain
Johnson
et
al.,
1987
(13)
(Continued)
916

PARENTAL
OCCUPATION
AND
CHILDHOOD
CANCER
Table
2.
Continued.
Number
of
Relative
exposed
Reference
Histology
Industry
or
occupation
Exposure
Time
frame
risk
95%
Cl
cases
Comments
Olsen
et
al.,
CNS
Auto
repair
At
time
of
5.90
S
5
1991
(23)
conception
Kuijten
et
al.,
Brain
Transportation
industry
Preconception
0.50
0.2-1.3
21
a
1992(9)
(astro-
During
pregnancy
0.10
0.0-0.6
16a
cytoma)
After
birth
0.60
0.2-1.4
30a
Motor
vehicle
Preconception
0.90
0.4-2.0
32a
exhausts,
more
During
pregnancy
0.70
0.2-2.6
12a
exposure
After
birth
1.00
0.0-78.4
2a
Motor
vehicle
Preconception
0.60
0.3-1.4
32a
exhausts,
less
During
pregnancy
0.50
0.2-1.3
23a
exposure
After
birth
0.70
0.3-1.7
27a
Abbreviations:
S,
significant;
NS,
not
significant;
NA,
not
available
from
published
report.
anumber
of
discordant
pairs.
[
calculated
by
the
authors
of
this
review.
No
maternal
occupation
or
exposure
was
consistently
associated
with
childhood
nervous
system
cancers.
Findings
from
individual
studies
were
associations
with
unspecified
chemical
exposures
(11);
occu-
pations
in
which
protective
clothing
or
equipment
was
used
(surrogate
for
expo-
sure)
(26);
unspecified
factory
work
(24);
nursing
(9);
and
slaughterhouses
and
meat
packers,
the
textile
industry,
child
care
workers,
and
kindergarten
teachers
(23).
Savitz
and
Chen
suggested
that
additional
study
is
needed
for
unspecified
chemical
exposures
among
mothers,
but
no
subse-
quent
studies
of
this
broad
exposure
have
been
performed
since
their
review.
Leukemia
and
Lymphoma
Significant
associations
have
been
found
in
multiple
studies
for
paternal
exposure
to
sol-
vents,
paints
and
pigments,
motor
vehicle-
related
occupations,
and
ionizing
radiation
(Table
3).
The
evidence
for
an
association
between
childhood
leukemia
and
paternal
exposure
to
solvents
is
quite
strong.
All
five
of
the
studies
addressing
solvent
exposures
have
reported
positive
associations.
A
number
of
the
relative
risks
were
quite
large
(i.e.,
greater
than
3.0),
and
despite
the
small
number
of
exposed
cases
in
many
of
the
studies,
several
were
statistically
significant
[solvents
in
general
(27),
chlorinated
sol-
vents
(28),
and
benzene,
carbon
tetrachlo-
ride,
and
trichloroethylene
(TCE)
(29)].
Buckley
et
al.
(27)
found
a
significant
trend
by
duration
of
exposure
for
undassified
sol-
vents,
but
could
not
identify
with
confi-
dence
the
specific
solvents
associated
with
acute
nonlymphocytic
leukemia
(ANLL)
risk.
The
association
between
childhood
cancer
and
solvents
is
an
added
concern
because
benzene
is
a
well-established
risk
factor for
adult
leukemia
and
other
solvents
are
suspected
leukemogens
(30).
Several
studies
have
evaluated
leukemia
risks
and
paternal
exposure
to
paints
and
pigments.
These
occupations
may
also
have
solvent
exposures.
A
majority
of
these
studies
reported
elevated
ORs
of
1.5
or
greater
(12,27,28,31),
with
two
reaching
statistical
significance.
The
two
studies
that
combined
leukemia
with
lymphoma
cases
found
no
association
(20,29).
A
number
of
occupational
investigations
have
noted
an
association
between
employment
as
a
painter
and
risk
of
leukemia
(30).
Savitz
and
Chen
also
concluded
that
exposure
to
paints
and
pigments
yielded
positive
results
that
were
relatively
consistent
and
that
fur-
ther
investigations
were
needed.
There
have
been
12
studies
of
child-
hood
leukemia
and
paternal
employment
in
occupations
related
to
motor
vehicles
or
involving
exposure
to
exhaust
gases.
Ele-
vated
risk
was
found
in
most
of
these
studies,
with
statistically
significant
findings
in
six.
Significant
associations
were
found
among
diverse
occupations
such
as
motor
vehicle
or
lorry
drivers
(12,32),
mechanics
and
gas
station
attendants
(17,27,33),
and
broader
groups
of
motor
vehicle-related
occupations
(18).
In
their
review
of
leukemia,
Linet
and
Cartwright
(30)
suggested
that
the
link
between
motor
vehi-
cle
occupations
and
adult
leukemia
may
be
due
to
benzene
and
other
components
in
engine
exhausts.
Ten
studies
have
examined
the
relation-
ship
between
paternal
exposure
to
ionizing
radiation
and
childhood
leukemia/lym-
phoma.
For
studies
that
provide
results
for
leukemia
alone
and
for
leukemia
combined
with
lymphoma,
only
the
leukemia
findings
are
tabulated.
Although
the
earlier
studies
found
no
significant
association
(27,31,34),
in
1990
Gardner
et
al.
(35)
reported
that
the
risk
of
childhood
leukemia
in
West
Cumbria,
England,
was
significantly
associ-
ated
with
paternal
employment
in
the
Sellafield
nuclear
fuel
reprocessing
plant,
particularly
for
fathers
with
high
radiation
dose
recordings
prior
to
their
child's
con-
ception.
However,
the
finding
was
specific
to
workers
in
the
village
of
Seascale
near
Sellafield
and
was
not
seen
among
the
off-
spring
of
other
Sellafield
workers
with
simi-
lar
preconception
doses.
McKinney
et
al.
(29)
and
Roman
et
al.
(36)
also
reported
significantly
increased
risks
for
paternal
exposure
to
ionizing
radiation,
although
the
population
in
McKinney's
study
over-
lapped
with
that
of
Gardner,
and
Roman's
study
was
based
on
small
numbers.
Four
other
studies
have
not
provided
support
for
this
hypothesis
(37-40).
Savitz
and
Chen
recommended
that
paternal
HC
exposure
be
studied
further
in
terms
of
its
link
with
childhood
leukemia.
With
the
evidence
from
more
recent
inves-
tigations,
we
do
not
find
compelling
evi-
dence
for
this
association.
As
with
nervous
system
cancers,
Fabia
and
Thuy
(17)
were
the
first
to
report
a
significant
relationship
between
hydrocarbon
exposure
and
child-
hood
leukemia.
Numerous
attempts
have
been
made
to
replicate
these
findings
(4,18-20,22,28,31,41).
There
have
been
no
significant
findings
despite
a
reasonable
number
of
exposed
cases.
Relative
risks
were
generally
close
to
1.0.
There
is
a
con-
siderable
range
of
possible
exposures
in
this
category.
This
range
and
the
variation
in
exposure
between
studies
diminishes
their
value
in
identifying
environmental
causes
of
cancer.
Unlike
the
nervous
system
cancers,
a
variety
of
maternal
occupational
exposures
have
been
found
to
be
significantly
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
917

COLT
AND
BLAIR
Table
3.
Childhood
leukemia
and
paternal
occupations
with
significant
findings
in
multiple
studies.
Number
of
Industry
or
Relative
exposed
Reference
Histology
occupation
Exposure
Time
frame
risk
95%
Cl
cases
Comments
Solvents
Buckley
et
al.,
1989
(27)
Feingold
et
al.,
1992
(22)
Shaw
et
al.,
1984
(54)
Lowengart
et
al.,
1987
(28)
ANLL
Solvents
ALL
Solvents
Leukemia
Benzene
Acute
leukemia
McKinney
et
al.,
Leukemia
1991
(29)
+
NHL
Feingold
et
al.,
1992
(22)
Lowengart
et
al.,
1987
(28)
ALL
Acute
leukemia
McKinney
et
al.,
Leukemia
1991
(29)
+NHL
Lowengart
et
al.,
1987
(28)
Acute
leukemia
Benzene
Benzene
Benzene
Xylene
Xylene
Toluene
MEK
Ever
2.00
1.2-3.8
Before
pregnancy
During
pregnancy
After
birth
During
pregnancy
At
birth
Year
before
conception
to
reference
date
Preconception
During
pregnancy
After
birth
During
pregnancy
Year
before
conception
to
reference
date
Preconception
During
pregnancy
After
birth
Year
before
conception
to
reference
date
Year
before
pregnancy
During
pregnancy
After
birth
Chlorinated
Year
before
solvents
pregnancy
During
pregnancy
After
birth
McKinney
et
al.,
Leukemia
1991
(29)
+NHL
Lowengart
et
al.,
1987
(28)
Acute
leukemia
Carbon
Year
before
tetrachloride
pregnancy
During
pregnancy
After
birth
Carbon
Preconception
tetrachloride
During
pregnancy
After
birth
TCE
Year
before
pregnancy
During
pregnancy
After
birth
2.20
2.10
1.50
1.70
[1.21]
NA
S
S
NS
0.4-8.2
57
OR
is
for
highest
exposure
duration
category;
p
trend
=
0.003.
NA
NA
NA
3
NS
205
NS
NA
5.81
1.7-26.4
12
Significance
remains
after
adjustment
for
other
exposures.
2.98
1.39
1.60
0.5-24.2
0.4-4.9
0.5-5.8
4
5
9
NA
NS
NA
6.86
3.24
3.24
NA
0.9-168
0.2-98.2
0.2-98.2
NS
1.70
NS
1.70
NS
3.00
0.8-17.2
2.20'
NS
2.20
NS
3.50
1.1-14.6
0.70
0.70
1.70
2.90
2.16
3.48
2.00
2.00
2.70
NS
NS
0.3-10.7
1.1-7.4
0.5-9.1
0.9-17.2
NS
NS
0.6-15.6
5
Not
independent
of
observation
for
benzene,
wood,
and
radiation.
2
2
NA
8a
8a
12a
13a
13a
18a
5a
5a
8a
13
5
6
ga
ga
11a
Significant
trend
with
frequency
of
use
(p=0.03).
Significant
trend
with
frequency
of
use
(p=
0.03).
OR
retains
significance
after
adjusting
for
other
exposures.
Not
independent
of
obser-
vation
for
benzene,
wood,
and
radiation.
(Continued)
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
918

PARENTAL
OCCUPATION
AND
CHILDHOOD
CANCER
Table
3.
Continued.
Number
of
Industry
or
Relative
exposed
Reference
Histology
occupation
Exposure
Time
frame
risk
95%
Cl
cases
Comments
McKinney
et
al.,
leukemia
TCE
Preconception
2.27
0.8-6.2
9
1991
(29)
+
NHL
Lowengart
et
al.,
Acute
PCE
1987
(28)
leukemia
Paints
and
pigments
Kwa
and
Fine,
Leukemia
Painters
HCs
1980
(20)
+
lymphoma
Hemminki
et
al.,
Leukemia
Painters
1981
(12)
Van
Steensel-Moll
ALL
Pigmi
et
al.,
1985
(31)
(dye
Lowengart
et
al.,
Acute
Spray
1987
(28)
leukemia
Dyes,
pigr
Buckley
et
al.,
ANLL
Painters
1989
(27)
McKinney
et
al.,
Leukemia
Paint
1991
(29)
+
NHL
dye
Motor
vehicle-related
occupations
Fabia
and
Thuy,
Leukemia
Motor
vehicle
mechanic,
HCs
1974
(17)
+
lymphoma
service
station
attendant
Hakulinen
et
al.,
Leukemia
Motor
vehicle
drivers
HCs
1976
(19)
+
lymphoma
Kwa
and
Fine,
Leukemia
Mechanics,
gas
station
HCs
1980
(20)
+
lymphoma
attendants
Hemminki
et
al.,
Leukemia
1981
(12)
Gold
et
al.,
Leukemia
1982
(18)
Vianna
et
al.,
Acute
1984
(33)
leukemia
Motor
vehicle
drivers
Motor
vehicle
drivers
Motor
vehicle
related
(driver,
mechanic,
service
station
attendant,
railroad
worker/engineer)
Drivers
High:
gas
station
attendants,
auto
or
truck
repairmen,
aircraft
maintenance
During
pregnancy
4.40
1.2-21.0
7
After
birth
2.66
0.8-9.2
7
After
birth
Infinity
0.2-infinity
2a
At
birth
0.90
During
pregnancy
1.50
lent
During
pregnancy
1.60
es)
y
paint
Year
before
1.40
pregnancy
During
pregnancy
2.20
After
birth
2.00
Year
before
3.50
ments
pregnancy
During
pregnancy
3.00
After
birth
4.50
Ever
7.00
ts
and
5I
At
birth
[2.03]
During
pregnancy
At
birth
During
pregnancy
Before
birth
After
birth
Motor
vehicle
Before
birth
exhaust
1.06
NS
7
OR
calculated
by
Savitz
and
Chen
(1990)
(2).
NS
12a
0.8-3.3
25
NS
31a
S
26a
Loses
significance
when
adjusted
for
chlorinated
solvents.
0.96-4.4
36a
Significant
trend
with
frequency
of
use
(p=
0.01).
Loses
significance
when
adjusted
for
chlorinated
solvents.
NS
ga
NS
8a
0.9-42.8
11
a
Significant
trend
with
frequency
of
use
(p=
0.04).
Loses
significance
when
adjusted
for
chlorinated
solvents.
S
7
NS
NA
Authors
say
"failed
to
confirm
association."
S
16
0.6-1.8
[35]
1.10
NS
21
ORs
calculated
by
Savitz
and
Chen
(1990)
(2).
1.00
NS
28
1.50
NS
96a
Results
are
for
entire
study
period.
1.90
S
45a
Results
are
for
1969-
1975
only.
0.75
NS
7a
Results
are
for
healthy
controls.
Infinity
S
6a
Results
are
for
cancer
controls.
1.50
NS
10a
Results
are
for
healthy
controls.
6.00
NS
7a
Results
are
for
cancer
controls.
2.43
S
24a
Results
are
for
control
group
A.
(Continued
on
next
page)
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
919

COLT
AND
BLAIR
Table
3.
Continued.
Number
of
Industry
or
Relative
exposed
Reference
Histology
occupation
Exposure
Time
frame
risk
95%
Cl
cases
Comments
Vianna
et
al.,
Acute
2.50
S
28a
Results
are
for
control
Van
Steensel-Moll
ALL
etal.,
1985
(31)
Shu
et
al.,
Leuke
1988
(43)
Buckley
et
al.,
ANLL
1989
(27)
Magnani
et
al.,
NHL
1990
(32)
McKinney
et
al.,
leukemia
1991
(29)
+
NHL
Roman
et
al.,
leukemia
1993
(36)
+
NHL
Moderate:
cab
driver,
Motor
vehicle
Before
birth
traveling
salesman,
exhaust
truck
or
bus
driver,
railroad
worker,
toll
booth
attendant,
highway
worker,
police
officer
Exhaust
gases
During
pregnancy
*mia
Transportation
equipment
operator
Nonauto
mechanics
Lorry
driver
Drivers
and
related
During
pregnancy
1.20
Ever
3.50
Before
birth
After
birth
Exhaust
fumes
At
birth
Before
birth
through
diagnosis
1.27
NS
group
B.
25a
Results
are
for
control
group
A.
3.75
S
19a
Results
are
for
control
group
B.
1.30
0.8-1.9
89
0.6-2.3
24
S
14
1.1-22.4
2
1.1-22.4
2
NS
NA
5.00
5.00
NA
0.60
0.1-2.0
3
1.30
0.4-3.2
7
Ionizing
radiation
Hicks
et
al.,
1984
(34)
Leukemia
Occupations
+
NHL
Industries
Van
Steensel-Moll
Leukemia
et
al.,
1985
(31)
Buckley
et
al.,
Leukemia
1989
(27)
Gardner
et
al.,
Leukemia
Nuclear
plant
1990
(35)
Urquhart
et
al.,
Leukemia
Nuclear
industry
1991
(37)
+
NHL
McKinney
et
al.,
Leukemia
1991
(29)
+
NHL
Kinlen
et
al.,
1993
(38)
Roman
et
al.,
1993
(36)
Leukemia
Nuclear
industry
Leukemia
Nuclear
+
NHL
industry
McLaughlin
et
al.,
Leukemia
Nuclear
industry
1993
(39)
(predominantly)
Sorahan
et
al.,
Leukemia
1993
(40)
Ionizing
radiation
Ionizing
radiation
Year
before
birth
0.78-1.41
NS
10-27
Range
of
ORs
for
different
control
groups
and
exposure
intensities.
0.76-1.09
NS
8-42
Range
of
ORs
for
different
control
groups
and
exposure
intensities.
Radioactivity
During
pregnancy
1.40
Ionizing
radiation
Ever
At
birth
External
ionizing
Preconception
radiation
Radiation
Radiation
Ionizing
radiation
0.6-3.5
13
1.90
NS
17
2.82
1.1-7.4
9
Area
controls.
2.03
0.7-5.9
9
Local
controls.
6.24
1.5-25.8
4
For
external
radiation
doses
exceeding
100
mSv.
Area
controls.
8.38
1.4-52.0
4
For
external
radiation
doses
exceeding
100
mSv.
Local
controls.
At
conception
0.58
0.1-2.6
3
Preconception
3.23
During
pregnancy
15.06
After
birth
3.08
Preconception 1.26
Ever
Preconception
Monitored
for
Ever
radiation
exposure
Preconception
Radiation
Preconception
External
ionizing
Preconception
radiation
Radionuclides
2.50
2.80
8.00
1.4-7.7
15
Study
population
overlaps
2.4-338
8
with
Gardner
et
al.
1.01-10.3
9
(1990)
(35).
0.6-3.9
1
1
0.6-9.0
4
0.6-10.5
4
1.4-54.6
4
9.00
1.0-107.8
3
0.87
0.2-2.3
6
1.45
2.75
0.8-2.8
29
0.9-8.6
1
1
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
1984
(33)
leukemia
NA,
Not
available
from
published
report;
S,
significant;
NS,
not
significant.
'Total
number
of
discordant
pairs.
[1],
calculated
by
the
authors
of
this
review.
920

PARENTAL
OCCUPATION
AND
CHILDHOOD
CANCER
associated
with
childhood
leukemia,
indud-
ing
personal
services,
textiles,
and
metals
(Table
4).
All
four
studies
that
looked
at
mothers
employed
in
the
personal
services
industry
found
significant
associations
with
childhood
leukemia.
The
specific
occupa-
tions
held
by
the
mothers,
however,
were
heterogeneous.
In
Lowengart's
study
(28),
mothers
in
the
personal
services
industry
were
employed
in
beauty
shops,
as
domestics
in
personal
households
or
other
lodgings,
or
in
laundries.
Van
Steensel-Moll
et
al.
(31)
focused
on
domestics
and
hotel
and
catering
employees.
Magnani
et
al.
(32)
observed
excesses
among
cleaners;
McKinney
et
al.
(29)
had
a
category
of
catering,
cleaning,
and
hairdressing.
The
presence
of
sig-
nificant
associations
between
leukemia
and
employment
in
the
personal
services
industry
before
birth,
but
not
during
the
postnatal
period,
may
provide
an
important
mechanistic
lead.
Three
of
the
four
studies
that
presented
data
on
the
textile
industry
found
sig-
nificant
risks
for
childhood
leukemia
(31,32,42).
Numbers
of
exposed
cases
were
small,
but
relative
risks
were
large.
This
lead
could
be
especially
important
given
the
large
number
of
women
employed
in
the
textile
industry
in
many
countries.
Only
two
studies
addressed
maternal
employment
in
occupations
likely
to
involve
exposure
to
metals,
and
both
found
significantly
elevated
risks
(27,43).
As
with
nervous
system
cancers,
Savitz
and
Chen
suggested
that
additional
study
is
needed
for
leukemia
and
unspecified
chem-
ical
exposures
among
mothers,
but
no
additional
studies
have
taken
place
since
their
review.
Urinary
System
Cancers
Savitz
and
Chen
did
not point
to
any
specific
paternal
exposures
warranting
fur-
ther
study
for
urinary
tract
cancers
and
only
one
study
of
urinary
system
cancers
has
been
published
since
their
review.
The
only
exposure
with
a
significant
finding
in
more
than
one
study
is
HCs
(Table
5).
With
the
possible
exception
of
Bunin
et
al.
(44)
(for
which
no
odds
ratio
was
provided),
the
studies
consistently
reported
elevated
risk
from
HC
exposure,
although
the
differ-
ences
are
not
always
statistically
significant.
Aromatic
HCs
have
been
dearly
established
risk
factors
for
adult
kidney
cancer
in
studies
of
coke-oven
workers
(45).
Kantor
et
al.
(46)
observed
an
increased
risk
for
Wilms
tumor
that
they
attributed
to
lead.
Other
studies
(44,47,48)
have
investigated
lead
as
a
possible
etiologic
Table
4.
Childhood
leukemia
and
maternal
occupations/exposures
with
significant
findings
in
multiple
studies.
Number
of
Industry
or
Relative
exposed
Reference
Histology
occupation
Exposure
Time
frame
risk
95%
Cl
cases
Comments
Personal
services
Van
Steensel-Moll
ALL
Domestics,
hotel,
During
pregnancy
2.80
1.3-5.7
24
et
al.,
1985
(31)
catering
After
birth
1.90
0.8-4.6
15
Lowengart
et
al.,
Acute
Personal
services
Year
before
2.70
S
12
1987(28)
leukemia
industry
(beauty
conception
to
shops,
domestics,
after
birth
laundries)
Magnani
et
al.,
ALL
Cleaner
Before
birth
3.00
1.1-8.4
8
1990
(32)
After
birth
0.60
0.1-3.0
2
McKinney
et
al.,
Leukemia
Catering,
cleaning,
Preconception
2.84
1.6-5.2
38
1991
(29)
+
NHL
hairdressing
During
pregnancy
3.12
1.1-8.7
Textiles
Van
Steensel-Moll
ALL
Textile
industry
During
pregnancy
4.20 1.0-17.7
8
etal.,
1985
(31)
Shu
et
al.,
Leukemia
Textile
workers
During
pregnancy
0.70
0.4-1.2
27
1988
(43)
and
tailors
Magnani
et
al.,
ANLL
Textile
spinner
Before
birth
10.10
2.2-46.0
2
1990
(32)
and
winder
After
birth
10.10
2.2-46.0 2
Textile
industry
Before
birth
1.90
0.5
-6.6
3
After
birth
4.30
1.2-15.0
3
Infante-Rivard
ALL
Sewing
at
home
Dust
During
pregnancy
5.50
1.2-24.8
12
et
al.,
1991
(42)
(cotton,
wool,
synthetic
fibers)
Metals
Shu
et
al.,
Leukemia
Metal
refining
and
During
pregnancy
2.60
0.9-7.7
8
1988
(43)
processing
workers
ALL
1.00
0.2-4.9
2
ANLL
4.60 1.3-17.2
5
Leukemia
Lead
1.90
0.5-6.9
5
Buckley
et
al.,
ANLL
Metal
manu-
Ever
4.50
S
10
Significant
trend
by
1989
(27)
facturing
duration
of
exposure.
Metal
dusts
Before
pregnancy
5.50
S
NA
During
pregnancy
3.00
NS
NA
After
birth
1.50
NS
NA
Abbreviations:
NA,
not
available
from
published
report;
S,
significant;
NS,
not
significant
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
921

COLT
AND
BLAIR
agent
for
Wilms
tumor
but
have
not
rep-
licated
the
Kantor
et
al.
(46)
finding.
Although
lead
causes
cancer
in
experimen-
tal
animals,
the
epidemiologic
evidence
is
weak
(49).
In
the
only
study
published
since
Savitz
and
Chen's
review,
significant
associations
were found
between
renal
cancers
and
paternal
employment
in
gen-
eral
manufacturing,
the
wood
and
furni-
ture
industry,
manufacturing
of
iron
and
metal
structures,
and
electrical
contracting
firms
(23).
Only
two
studies
have
looked
at
mater-
nal
occupations
and
childhood
urinary
tract
cancers.
There
have
been
isolated
sig-
nificant
findings
for
Wilms
tumor
and
maternal
exposure
to
aromatic
amines
(44);
and
for
renal
cancer
and
education,
health
and
welfare,
health
departments,
and
practicing
dentists
(23).
Discussion
Although
several
occupation/cancer
combinations
are
intriguing
and
clearly
deserve
further
attention,
the
evidence
for
any
association
falls
short
of
certainty.
The
strongest
evidence
for
an
association
between
fathers'
occupations
and
the
risk
of
childhood
cancer
is
for
exposure
to
sol-
vents
and
paints
and
the
risk
of
leukemias
and
cancers
of
the
nervous
system.
These
associations
are
biologically
plausible
given
findings
from
experimental
investi-
gations
and
epidemiologic
studies
of
adult
cancer
(49).
For
nervous
system
cancers,
the
evidence
is
less
convincing
for
other
paternal
occupa-
tions.
Despite
the
large
number
of
positive
findings
in
EMF
studies,
investigators
have
hesitated
to
conclude
that
the
association
is
real.
The
biologic
plausibility
is
uncertain
(25)
and
the
findings
are
inconsistent
for
direct
exposures
to
children
as
well
as
adults.
It
is
also
possible
that
positive
findings
are
indicative
of
exposures
other
than
EMF
in
these
occupations.
Employment
in
the
elec-
trical
or
electronics
industry
may
entail
exposure
to
various
chemicals
including
sol-
vents,
soldering
fumes,
epoxy,
phenolic
resins,
polychlorinated
biphenyls,
and
met-
als
(beryllium,
nickel,
lead,
zinc,
platinum,
tellurium)
(7,8,25).
Epidemiologic
studies
provide
strong
evidence
for
a
link
between
childhood
leukemia
and
paternal
exposure
to
solvents.
This
is
consistent
with
other
experimental
findings
and
epidemiologic
studies
among
adults
(49).
Children
may
be
exposed
to
solvents
that
their
parents
bring
home
from
the
workplace
on
their
skin
or
clothes,
or
from
their
exhaled
air.
Chlorinated
solvents
have
been
found
in
the
exhaled
air
of
work-
ers
a
number
of
hours
after
exposure,
and
perchloroethylene
was
detected
in
the
breast
milk
and
blood
of
a
mother
who
vis-
ited
her
husband
daily
at
a
dry
cleaning
establishment
(28).
Painters,
printers,
and
workers
in
motor
vehicle-related
occupations,
which
are
fairly
consistently
linked
with
childhood
leukemia,
may
have
occupational
expo-
sure
to
solvents.
Painters
are
typically
exposed
to
a
number
of
different
solvents
(28),
and
workers
in
motor
vehicle-
related
occupations
(mechanics,
gas
sta-
tion
attendants,
drivers)
are
exposed
to
gasoline
and
gasoline exhaust,
which
con-
tain
benzene
(22,29,43).
However,
these
occupations
involve
exposure
to
a
variety
of
other
chemicals
as
well.
For
example,
gasoline
contains
dichloroethane
and
dibromomethane
(12),
and
the
particulate
fraction
of
exhaust
fumes
contains
aro-
matic
compounds
such
as
benzo[a]pyrene
that
are
capable
of
producing
tumors
in
lower
animals
(33).
Although
there
is
strong
evidence
that
children
directly
exposed
to
ionizing
radia-
tion
are
at
increased
risk
for
developing
leukemia,
the
evidence
for
a
link
between
childhood
leukemia
and
paternal
radiation
exposure
is
weak.
Gardner
et
al.
(35)
were
the
first
to
report
such
an
association,
but
the
elevated
risk
among
Sellafield
plant
workers
was
found
only
among
those
living
in
one
particular
villlage.
McKinney's
study
population
(29)
overlapped
with
that
of
Gardner's,
and
Roman's
results
(36)
were
based
on
a
small
number
of
cases.
Most
of
the
studies
have
not
found
an
association.
In
a
review
of
this
topic,
Little
et
al.
(50)
and
Doll
et
al.
(51)
con-
cluded
that
the
inconsistency
not
only
with
other
epidemiologic
data
but
also
with
experimental
data
makes
it
highly
unlikely
Table
5.
Childhood
urinary
tract
cancers
and
paternal
occupations
with
significant
findings
in
multiple
studies.
Number
of
Relative
exposed
Reference
Histology
Industry
or
occupation
Exposure
Time
frame
risk
95%
Cl
cases
Comments
Hydrocarbons
Kantor
et
al.,
Wilms
Machinist,
cleaner,
embalmer,
HCs
(some
At
birth
2.40
1.1-5.7
24
The
authors
conclude
1979
(46)
driver,
motor
vehicle
mechanic,
also
involve
that
increased
risk
service
station
attendant
lead)
is
due
to
lead
rather
than
HCs.
Machinist,
cleaner,
embalmer
HCs
only
1.40
NS
7
Driver,
motor
vehicle
mechanic,
HCs
and
3.40
NS
17
service
station
attendant
lead
Kwa
and
Fine,
Urinary
Mechanics,
gas
station
HCs
2.50
S
10
1980
(20)
tract
attendants,
machinists
Sanders
at
al.,
Kidney
Miners,
engineering
and
allied
HCs
At
child's
1.19
NS
79
1981
(4)
trades,
textile
workers,printers,
death
painters,decorators,
dry
cleaners,
motor
vehicle
drivers
Wilkins
and
Sinks,
Wilms
Motor
vehicle
mechanic,
service
HCs
At
birth
1.4
0.7-2.7
19
1984
(47)
station
attendant,
driver/heavy
equipment
operator,
metal
worker/machinist,
lumberman,
miner,
painter,
printer,
leather
worker,
factory
worker
Bunin
et
al.,
Wilms
HCs
Age
18-
NA
NS
NA
1989
(44)
after
birth
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
922

PARENTAL
OCCUPATION
AND
CHILDHOOD
CANCER
that
the
association
observed
in
Gardner's
study
represents
a
causal
relationship.
Studies
have
not
shown
elevated
leukemia
risks
among
children
of atomic
bomb
sur-
vivors,
although
the
relationship
between
paternal
irradiation
prior
to
conception
and
cancer
in
the
offspring
has
not
been
well
studied
in
this
cohort.
Studies
of
maternal
occupations
raise
the
possibility
that
mothers
employed
in
per-
sonal
services
and
textiles
occupations
may
place
their
children
at
increased
risk
for
leukemia.
The
specific
exposures
that
may
be
responsible
are
unknown.
Personal
services
occupations
are
heterogeneous.
Women
in
the
textile
industry
may
be
exposed
to
a
variety
of
substances
including
organic
dusts
and
fibers,
dyes
in
synthetic
fibers,
and
oil,
grease,
and
EMF
from
their
sewing
machines
(42,52).
These
findings
need
fir-
ther
evaluation,
given
the
large
number
of
women
employed
in
these
industries.
Results
from
studies
of
childhood
cancer
and
parental
occupation
must
be
evaluated
in
light
of
their
strengths
and
weaknesses.
Epidemiologic
studies
of
parental
occupa-
tion
and
childhood
cancer
face
many
of
the
same
methodological
challenges
as
studies
of
adult
occupation
and
cancer.
In
particular,
assessing
exposures
to
specific
workplace
agents
is
problematic
when
the
only
avail-
able
information
is
a
job
or
industry
tide,
as
is
the
case
with
virtually
all
of
the
childhood
cancer
studies
conducted
to
date.
Workers
with
identical
job
tides
can
have
vastly
dif-
ferent
exposures
depending
on
their
specific
activities
and
the
extent
to
which
exposure
controls
(e.g.,
protective
equipment,
ventila-
tion)
are
used.
The
impact
on
estimates
of
relative
risk
from
reliance
on
simple
and
less
accurate
exposure
assessment
procedures
is
clear:
it
would
tend
to
bias
estimates
of
relative
risks
toward
the
null
(53).
An
addi-
tional
limitation
of
the
use
of
simple,
quali-
tative
exposure
assessments
is
that
it
is
more
difficult
to
evaluate
exposure-response
rela-
tionships,
a
key
criterion
for
the
assessment
of
causality.
Exposure
assessment
in
childhood
cancer
studies
is
further
hampered
by
our
lack
of
understanding
regarding
the
relevant
time
frame
of
exposure.
In
most
circum-
stances
we
do
not
know
whether
exposures
relevant
to
the
disease
process
occur
prior
to
conception
(i.e.,
germ
cell
effects),
during
pregnancy
(i.e.,
transplacentally,
from
expo-
sures
experienced
by
the
mother
at
the
workplace
or
from
paternal
transfer
of
sub-
stances
from
the
workplace
to
the
home),
or
after
birth
(i.e.,
substances
carried
home
by
either
parent).
Studies
should
be
designed
to
focus
on
all
three
time
periods.
Little
is
known
about
the
effectiveness
of
transpla-
cental
exposures
or
on
the
transfer
of
chemi-
cals
from
the
workplace
to
the
home.
It
surely
varies
by
type
of
parental
exposure
and
by
workplace
practices
such
as
shower-
ing
or
changing
back
to
street
clothes
before
going
home,
yet
these
factors
have
not
been
taken
into
account
in
any
of
the
studies
so
far.
On
the
other
hand,
although
the
rele-
vant
time
frame
of
exposure
is
uncertain
for
children,
it is
likely
narrower
than
it
is
for
adults,
which makes
exposure
assessment
easier.
Except
for
the
preconception
mecha-
nisms,
childhood
cancer
involves
exposure
for
at
most
a
couple
of
decades
(i.e.,
from
conception
to
the
late
teenage
years),
whereas
the
relevant
exposure
time
frame
for
adult
cancers
typically
spans
several
decades.
If
the
relevant
exposures
are
pre-
conceptional
(germ
cell
effects),
the
time
frame
can,
of
course,
be
as
long
as
the
par-
ent's
life,
or
may
even
extend
to
the
prenatal
period
for
the
mother.
Small
numbers
of
exposed
cases
in
studies
of
occupation
and
child
cancer
make
it
difficult
to
achieve
stable
results.
Some
investigators
have
addressed
this
problem
by
aggregating
different
jobs
believed
to
have
common
exposures.
This
approach
can
increase
numbers
and
lead
to
more
stable
results,
and
also
minimizes
contamination
of
the
unexposed
group
with
jobs
that
have
the
exposure
of
inter-
est.
On
the
other
hand,
it
may
increase
misclassification
of
exposure
by
combining
jobs
with
different
exposures
(2).
As
with
studies
of
adult
cancer
and
occupation,
as
the
number
of
studies
and
comparisons
increases,
the
number
of
significantly
elevated
relative
risks
that
are
due
strictly
to
chance
also
increases.
Evaluation
of
consistency
across
studies,
however,
tends
to
address
this
issue.
A
false
impression
of
a
positive
association
could
also
arise
because
of
selective
report-
ing
of
study
results
by
authors.
In
each
of
the
48
studies
reviewed
here,
it
was
possi-
ble
to
evaluate
childhood
cancer
risks
from
parental
employment
in
numerous
occu-
pations
and
from
exposure
to
a
variety
of
substances.
Only
a
small
number
of
these
comparisons,
however,
is
reported
in
any
paper.
Thus,
selective
reporting
is
occur-
ring.
It
seems
reasonable
to
assume
that
authors
may
tend
to
preferentially
report
positive
findings.
With
such
a
bias,
the
lit-
erature
may
appear
more
consistently
positive
than
appropriate.
Despite
these
limitations,
epidemio-
logic
studies
have
provided
sufficient
evi-
dence
that
certain
parental
exposures
may
be
harmful
to
their
children.
Paternal
exposures
to
paints
(nervous
system
cancers
and
leukemia),
solvents
(leukemia),
and
employment
in
motor
vehide-related
occu-
pations
(leukemia)
clearly
deserve
further
study.
To
more
clearly
evaluate
the
impor-
tance
of
these
and
other
exposures,
more
sophisticated
assessment
approaches
need
to
be
employed
in
future
investigations.
Improvements
are
needed
in
four
areas.
First,
more
careful
attention
must
be
paid
to
maternal exposures
because
of
the
potential
for
transfer
of
chemicals
to
the
child
during
pregnancy
and
nursing.
Second,
studies
must
employ
sophisticated
exposure
assessment
techniques
capable
of
developing
quantitative
estimates
of
spe-
cific
chemicals.
Third,
careful
attention
must
be
paid
to
the
postulated
mechanism
and
route
of
exposure.
To
the
extent
possi-
ble,
exposures
should
be
assessed
specifi-
cally
for
the
preconception,
prenatal,
and
postnatal
periods.
Finally,
if
postnatal
exposures
are
evaluated,
studies
need
to
provide
evidence
that
the
exposure
is
actu-
ally
transferred
from
the
workplace
to
the
child's
environment.
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Vol
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Supplement
3
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June
1998

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Environmental
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Supplement
3
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June
1998
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