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Gene-environment interaction involved in cholangiocarcinoma in the Thai population: polymorphisms of DNA repair genes, smoking and use of alcohol.
[cholangiocarcinoma]
Cholangiocarcinoma
(
CCA
)
is
the
most
common
malignancy
in
a
Northeast
Thai
population
.
Smoking
and
alcohol
drinking
are
associated
with
the
production
of
free
radical
intermediates
,
which
can
cause
several
types
of
DNA
lesions
.
Reduced
repair
of
these
DNA
lesions
would
constitute
an
important
risk
factor
for
cancer
development
.
We
therefore
examined
whether
polymorphisms
in
DNA
base-excision
repair
(
BER
)
genes
,
XRCC
1
G
399
A
and
OGG
1
C
3
26
G
,
were
associated
with
CCA
risk
and
whether
they
modified
the
effect
of
smoking
and
alcohol
drinking
in
the
Thai
population
.
A
nested
case-control
study
within
the
cohort
study
was
conducted
:
219
participants
with
primary
CCA
were
each
matched
with
two
non-
cancer
controls
from
the
same
cohort
on
sex
,
age
at
recruitment
and
the
presence
/
absence
of
Opisthorchis
viverrini
eggs
in
stools
.
Smoking
and
alcohol
consumption
were
assessed
on
recruitment
.
Polymorphisms
in
BER
genes
were
analysed
using
a
PCR
with
high
-resolution
melting
analysis
.
The
associations
were
assessed
using
conditional
logistic
regression
.
Our
results
suggest
that
,
in
the
Thai
population
,
polymorphisms
in
XRCC
1
and
OGG
1
genes
,
particularly
in
combination
,
are
associated
with
increased
susceptibility
to
CCA
,
and
that
their
role
as
modifiers
of
the
effect
of
smoking
and
alcohol
consumption
influences
the
risk
of
CCA
.
Better
ways
of
reducing
habitual
smoking
and
alcohol
consumption
,
targeted
towards
subgroups
which
are
genetically
susceptible
,
are
recommended
.
CCA
is
a
multifactorial
disease
,
and
a
comprehensive
approach
is
needed
for
its
effective
prevention
.
This
approach
would
also
have
the
additional
advantage
of
reducing
the
onset
of
other
cancers
.
Diseases
Validation
Diseases presenting
"which can cause several types of dna lesions"
symptom
cholangiocarcinoma
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