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A Functional TNFAIP2 3'-UTR rs8126 Genetic Polymorphism Contributes to Risk of Esophageal Squamous Cell Carcinoma.
[esophageal squamous cell carcinoma]
Accumulated
evidences
demonstrated
that
single
nucleotide
polymorphisms
(
SNPs
)
in
mRNA
3
'
-
untranslated
region
(
3
'
-
UTR
)
may
impact
microRNAs
(
miRNAs
)
-
mediated
expression
regulation
of
oncogenes
and
tumor
suppressors
.
There
is
a
TNFAIP
2
3
'
-
UTR
rs
8126
T
>
C
genetic
variant
which
has
been
proved
to
be
associated
with
head
and
neck
cancer
susceptibility
.
This
SNP
could
disturb
binding
of
miR-
184
with
TNFAIP
2
mRNA
and
influence
TNFAIP
2
regulation
.
However
,
it
is
still
unclear
how
this
polymorphism
is
involved
in
development
of
esophageal
squamous
cell
carcinoma
(
ESCC
)
.
Therefore
,
we
hypothesized
that
the
functional
TNFAIP
2
rs
8126
SNP
may
affect
TNFAIP
2
expression
and
,
thus
,
ESCC
risk
.
We
investigated
the
association
between
the
TNFAIP
2
rs
8126
variant
and
ESCC
risk
as
well
as
the
functional
relevance
on
TNFAIP
2
expression
in
vivo
.
Genotypes
were
determined
in
a
case-control
set
consisted
of
588
ESCC
patients
and
600
controls
.
The
allele-
specific
regulation
on
TNFAIP
2
expression
by
the
rs
8126
SNP
was
examined
in
normal
and
cancerous
tissue
specimens
of
esophagus
.
We
found
that
individuals
carrying
the
rs
8126
CC
or
CT
genotype
had
an
OR
of
1
.
89
(
95
%
CI
 
=
 
1
.
23
-
2
.
85
,
P
 
=
 
0
.
003
)
or
1
.
38
(
95
%
CI
 
=
 
1
.
05
-
1
.
73
,
P
 
=
 
0
.
017
)
for
developing
ESCC
in
Chinese
compared
with
individual
carrying
the
TT
genotype
.
Carriers
of
the
rs
8126
CC
and
CT
genotypes
had
significantly
lower
TNFAIP
2
mRNA
levels
than
those
with
the
TT
genotypes
in
normal
esophagus
tissues
(
P
<
0
.
05
)
.
Our
data
demonstrate
that
functional
TNFAIP
2
rs
8126
genetic
variant
is
a
ESCC
susceptibility
SNP
.
These
results
support
the
hypothesis
that
genetic
variants
interrupting
miRNA-mediated
gene
regulation
might
be
important
genetic
modifiers
of
cancer
risk
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated