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Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
[waldenström macroglobulinemia]
Non-
Hodgkin
lymphoma
(
NHL
)
comprises
biologically
and
clinically
heterogeneous
subtypes
.
Previously
,
study
size
has
limited
the
ability
to
compare
and
contrast
the
risk
factor
profiles
among
these
heterogeneous
subtypes
.
We
pooled
individual-level
data
from
17
471
NHL
cases
and
23
096
controls
in
20
case-control
studies
from
the
International
Lymphoma
Epidemiology
Consortium
(
InterLymph
)
.
We
estimated
the
associations
,
measured
as
odds
ratios
,
between
each
of
11
NHL
subtypes
and
self-reported
medical
history
,
family
history
of
hematologic
malignancy
,
lifestyle
factors
,
and
occupation
.
We
then
assessed
the
heterogeneity
of
associations
by
evaluating
the
variability
(
Q
value
)
of
the
estimated
odds
ratios
for
a
given
exposure
among
subtypes
.
Finally
,
we
organized
the
subtypes
into
a
hierarchical
tree
to
identify
groups
that
had
similar
risk
factor
profiles
.
Statistical
significance
of
tree
partitions
was
estimated
by
permutation-based
P
values
(
P
NODE
)
.
Risks
differed
statistically
significantly
among
NHL
subtypes
for
medical
history
factors
(
autoimmune
diseases
,
hepatitis
C
virus
seropositivity
,
eczema
,
and
blood
transfusion
)
,
family
history
of
leukemia
and
multiple
myeloma
,
alcohol
consumption
,
cigarette
smoking
,
and
certain
occupations
,
whereas
generally
homogeneous
risks
among
subtypes
were
observed
for
family
history
of
NHL
,
recreational
sun
exposure
,
hay
fever
,
allergy
,
and
socioeconomic
status
.
Overall
,
the
greatest
difference
in
risk
factors
occurred
between
T
-
cell
and
B-
cell
lymphomas
(
P
NODE
<
1
.
0
×
10
(
-
4
)
)
,
with
increased
risks
generally
restricted
to
T
-
cell
lymphomas
for
eczema
,
T
-
cell-activating
autoimmune
diseases
,
family
history
of
multiple
myeloma
,
and
occupation
as
a
painter
.
We
further
observed
substantial
heterogeneity
among
B-
cell
lymphomas
(
P
NODE
<
1
.
0
×
10
(
-
4
)
)
.
Increased
risks
for
B-
cell-activating
autoimmune
disease
and
hepatitis
C
virus
seropositivity
and
decreased
risks
for
alcohol
consumption
and
occupation
as
a
teacher
generally
were
restricted
to
marginal
zone
lymphoma
,
Burkitt
/
Burkitt-like
lymphoma
/
leukemia
,
diffuse
large
B-
cell
lymphoma
,
and
/
or
lymphoplasmacytic
lymphoma
/
Waldenström
macroglobulinemia
.
Using
a
novel
approach
to
investigate
etiologic
heterogeneity
among
NHL
subtypes
,
we
identified
risk
factors
that
were
common
among
subtypes
as
well
as
risk
factors
that
appeared
to
be
distinct
among
individual
or
a
few
subtypes
,
suggesting
both
subtype-
specific
and
shared
underlying
mechanisms
.
Further
research
is
needed
to
test
putative
mechanisms
,
investigate
other
risk
factors
(
eg
,
other
infections
,
environmental
exposures
,
and
diet
)
,
and
evaluate
potential
joint
effects
with
genetic
susceptibility
.
Diseases
Validation
Diseases presenting
"factor profiles among these heterogeneous subtypes"
symptom
waldenström macroglobulinemia
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