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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
"autoimmune disease"
symptom
acute rheumatic fever
coats disease
familial hypocalciuric hypercalcemia
familial mediterranean fever
harlequin ichthyosis
inclusion body myositis
kabuki syndrome
malignant atrophic papulosis
omenn syndrome
sneddon syndrome
waldenström macroglobulinemia
wiskott-aldrich syndrome
This symptom has already been validated