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Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus: a mendelian randomization study.
[esophageal adenocarcinoma]
Data
from
observational
studies
suggest
that
body
mass
index
(
BMI
)
is
causally
related
to
esophageal
adenocarcinoma
(
EAC
)
and
its
precursor
,
Barrett
's
esophagus
(
BE
)
.
However
,
the
relationships
may
be
affected
by
bias
and
confounding
.
We
used
data
from
the
Barrett
's
and
Esophageal
Adenocarcinoma
Genetic
Susceptibility
Study
:
999
patients
with
EAC
,
2061
patients
with
BE
,
and
2169
population
controls
.
We
applied
the
two
-
stage
control
function
instrumental
variable
method
of
the
Mendelian
randomization
approach
to
estimate
the
unbiased
,
unconfounded
effect
of
BMI
on
risk
of
EAC
and
BE
.
This
was
performed
using
a
genetic
risk
score
,
derived
from
29
genetic
variants
shown
to
be
associated
with
BMI
,
as
an
instrument
for
lifetime
BMI
.
A
higher
score
indicates
propensity
to
obesity
.
All
tests
were
two
-sided
.
The
genetic
risk
score
was
not
associated
with
potential
confounders
,
including
gastroesophageal
reflux
symptoms
and
smoking
.
In
the
instrumental
variable
analyses
(
IV
)
,
EAC
risk
increased
by
16
%
(
IV-odds
ratio
[
OR
]
=
1
.
16
,
95
%
confidence
interval
[
CI
]
=
1
.
01
to
1
.
33
)
and
BE
risk
increased
by
12
%
(
IV-
OR
=
1
.
12
,
95
%
CI
=
1
.
00
to
1
.
25
)
per
1
kg
/
m
(
2
)
increase
in
BMI
.
BMI
was
statistically
significantly
associated
with
EAC
and
BE
in
conventional
epidemiologic
analyses
.
People
with
a
high
genetic
propensity
to
obesity
have
higher
risks
of
esophageal
metaplasia
and
neoplasia
than
people
with
low
genetic
propensity
.
These
analyses
provide
the
strongest
evidence
to
date
that
obesity
is
independently
associated
with
BE
and
EAC
,
and
is
not
due
to
confounding
or
bias
inherent
in
conventional
epidemiologic
analyses
.
Diseases
Validation
Diseases presenting
"obesity"
symptom
acute rheumatic fever
adrenal incidentaloma
aniridia
aromatase deficiency
carcinoma of the gallbladder
cohen syndrome
congenital adrenal hyperplasia
cushing syndrome
cystinuria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
heparin-induced thrombocytopenia
kabuki syndrome
monosomy 21
phenylketonuria
primary hyperoxaluria type 1
sneddon syndrome
werner syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated