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Homozygous GNAS 393C-Allele Carriers with Locally Advanced Esophageal Cancer Fail to Benefit from Platinum-Based Preoperative Chemoradiotherapy.
[esophageal carcinoma]
Currently
,
patients
with
locally
advanced
esophageal
cancer
receive
neoadjuvant
chemoradiotherapy
but
only
about
half
of
these
patients
benefit
from
this
treatment
.
GNAS
T
393
C
has
been
shown
to
predict
the
postoperative
course
in
solid
tumors
and
may
therefore
be
useful
for
treatment
stratification
.
The
aim
of
the
present
study
was
to
determine
if
the
single
-nucleotide
polymorphism
GNAS
T
393
C
can
be
used
for
treatment
stratification
in
esophageal
cancer
patients
.
A
total
of
596
patients
underwent
surgical
resection
for
esophageal
carcinoma
from
1996
to
2008
;
279
patients
received
chemoradiotherapy
prior
to
surgery
(
RTX-SURG
group
)
.
All
patients
and
a
reference
group
of
820
healthy
White
individuals
were
genotyped
for
GNAS
T
393
C
.
The
5
-
year
-survival
rate
for
the
317
patients
who
underwent
esophagectomy
as
initial
treatment
(
SURG
group
)
was
57
%
for
homozygous
C-
allele
carriers
(
n
=
99
)
and
43
%
for
T
-
allele
carriers
(
n
=
218
;
log-
rank
test
p
=
0
.
025
)
.
Multivariate
analysis
revealed
the
GNAS
T
393
C
genotype
(
p
=
0
.
034
)
,
pT
(
p
<
0
.
001
)
,
pN
(
p
<
0
.
001
)
and
age
(
p
<
0
.
001
)
as
prognostic
of
survival
.
Homozygous
C-
allele
carriers
with
a
locally
advanced
tumor
stage
(
cT
3
/
T
4
,
n
=
129
)
in
the
SURG
group
had
a
5
-
year
survival
rate
of
37
%
,
which
,
remarkably
,
exceeded
the
5
-
year
survival
rate
of
30
%
for
the
entire
RTX-SURG
group
(
n
=
279
)
.
In
the
RTX-SURG
group
,
the
GNAS
T
393
C
genotype
did
not
show
any
prognostic
significance
.
Patients
with
a
locally
advanced
esophageal
cancer
and
an
homozygous
GNAS
393
C
genotype
do
not
benefit
from
platinum-based
neoadjuvant
chemoradiotherapy
,
indicating
that
these
patients
should
be
treated
by
alternative
treatment
strategies
.
Diseases
Validation
Diseases presenting
"tumor stage"
symptom
carcinoma of the gallbladder
cholangiocarcinoma
cushing syndrome
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
wiskott-aldrich syndrome
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