Biology Reference
In-Depth Information
arm, response rates were 47.3% for those with low
ERCC1 levels and 26.1% for those with high levels.
127
A study investigated whether ERCC1 polymor-
phisms had an effect on response to chemotherapy
and survival in patients with NSCLC treated with
cisplatin combination chemotherapy. The median
survival time in patients showing C/C genotype at
codon 118 was 486 days compared to 281 days in
patients with the variant genotype (T/T or C/T).
128
In
another study, a statistically significant association
between the C8092A polymorphism and overall
survival was shown. The median survival times of 22.3
(C/C) and 13.4 (C/A or A/A) months, respectively,
suggests that any copies of the A allele were associated
with poor outcome.
129
Similar results have been
observed in other studies, although they have not shown
an association between ERCC1 T19007C SNP and prog-
nosis.
130
Another study suggests that carrying at least
one ERCC1 8092A allele is associated with a
significantly associated with a good response to irinote-
can-based chemotherapy in a sample of 33 patients with
metastatic colorectal cancer.
137
The T19007C polymor-
phism may be associated with reduced ERCC1 mRNA
expression and protein levels.
138
The objective response
rate to oxaliplatin in combination with 5-fluorouracil
(5-FU) was significantly higher in the T/T genotype
group compared with the C/T and the C/C genotype
groups (61.9%, 42.3%, and 21.4%, respectively).
139
In
another study, patients with the C/C genotype had
a median survival of 15.3 months whereas those with
C/T and T/T genotypes had a median survival of 11.1
months.
140
This was also confirmed in a separate study
in metastatic colorectal cancer patients receiving 5-FU/
oxaliplatin combination chemotherapy.
111
ERCC1 19007
T
C has been associated with a poor prognosis in
patients with colorectal cancer
>
receiving adjuvant
chemotherapy.
108
2-fold
increase in grade 3 or 4 gastrointestinal toxicity among
platinum-treated non-small cell lung cancer patients.
131
The C to A change of ERCC1 Gln504Lys polymorphism
has been shown to be associated with reduced response
to platinum-based chemotherapy.
132
Not all studies have repeated these results and
another study investigating patients with NSCLC found
no association between polymorphisms in ERCC1
C8092A and codon 118 and response to cisplatin-based
chemotherapy.
133
Two recent meta-analyses have
attempted to address the discrepancies described above;
however these have both demonstrated discordant
results. One meta-analysis of 12 studies in patients
receiving platinum-based chemotherapy for NSCLC
has concluded that polymorphism of ERCC1 C118T is
significantly associated with sensitivity to platinum-
based chemotherapy. The overall response rate for the
C/C wild-type genotype was found to be 2.17 (95%
confidence interval, 1.43-3.33: P
>
ERCC1 and Upper GI Cancers
In gastric cancer, low mRNA levels correlated to
objective response to neoadjuvant cisplatin/5FU chemo-
therapy. In addition, there was an inverse relation
between ERCC1 mRNA levels in tumor tissues and
patient survival in that study.
141
An immunohistochem-
ical study of ERCC1 protein expression in advanced
gastric cancer patients treated with 5-FU/oxaliplatin
chemotherapy has demonstrated that patients without
ERCC1 expression were more likely to respond to
chemotherapy and have significantly longer median
overall survival.
142
Another study of 32 patients with
advanced gastric cancer treated with cisplatin-based
chemotherapy found no association between ERCC1
expression by immunohistochemistry staining and
survival. A higher response rate was seen in the
ERCC1-negative patients but this was not statistically
significant.
143
In locally advanced esophageal cancer, higher ERCC1
mRNA expression correlated to poor response to neoad-
juvant radiochemotherapy (cisplatin, 5-fluorouracil, and
36 Gy of radiation).
144
Another study of chemoradio-
therapy followed by surgery in esophageal cancer has
shown that high ERCC1 mRNA expression is a predictor
of decreased survival and increased risk of cancer recur-
rence.
145
However, in a further study of chemoradiother-
apy for esophageal squamous-cell carcinoma ERCC1
expression was not associated with response to
treatment.
146
ERCC1 nuclear expression has been shown to be corre-
lated with a poor histological response (TRG 4 or 5) to
platinum-based neoadjuvant chemotherapy in patients
with gastro-esophageal adenocarcinoma. Both poor
disease-specific and overall survival was observed in
these individuals.
147
0.000) when compared
with the heterozygous C/T and T/T genotype.
134
However, another meta-analysis of 2097 patients and
17 studies of patients with NSCLC treated with plat-
inum-based regimens found no evidence to support the
use of ERCC1 C118T or C8092A SNPs as predictors of
prognosis with platinum-based chemotherapy.
135
ΒΌ
ERCC1 and Colorectal Cancers
Intra-tumoral ERCC1 mRNA expression level may be
a predictive marker of survival for irinotecan-resistant
metastatic colorectal cancer receiving 5-FU and oxalipla-
tin combination chemotherapy; patients whose tumors
had low ERCC1 mRNA expression had a significantly
longer median survival than those with high ERCC1
expression.
136
In contrast, another study showed that
high intra-tumoral mRNA levels of ERCC1 were
