Considerable inter-individual differences in therapeutic and adverse effects still
exist among NSCLC patients even with the same pathological type and stage,
receiving the same chemotherapy.
The polymorphic Ile105Val of GSTP1 is linked to the platinum metabolism, and
that RRM1 expression, related with the efficacy of gemcitabine, is affected by
RRM1 C37A-T524C polymorphism.
The association of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms
with response and toxicity to gemcitabine-cisplatin combination chemotherapy is
Previous studies showed that genetic polymorphisms of glutathione S-transferase P1
(GSTP1) were involved in glutathione metabolism and genetic polymorphisms of
ribonucleotide reductase (RRM1) were correlated with DNA synthesis. Here we
explored the effects of these polymorphisms on the chemosensitivity and clinical
outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with
DNA sequencing was used to evaluate genetic polymorphisms of GSTP1 Ile105Val
and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin
regimens. Clinical response was evaluated according to RECIST criteria after 2 cycles
of chemotherapy and toxicity was assessed by the 1979 WHO criteria (Acute and
subacute toxicity graduation criteria in chemotherapeutic agents).
The result showed that there was no significant difference in genotype frequency
distribution of GSTP1 Ile105Val polymorphism between sensitive group and
non-sensitive group (P>0.05). But for RRM1 C37A-T524C genotype, sensitive group
had higher proportion of high efficiency genotype than non-sensitive group
(P=0.0087). And according to the joint detection of GSTP1 Ile105Val and RRM1
C37A-T524C polymorphisms, the proportion of type A (A/A+high efficiency
genotype) was significantly higher in sensitive group than that in non-sensitive group(P=0.0088). Toxicity showed no correlation with genotypes between the groups
In conclusion, compared with single detection of genetic polymorphisms of GSTP1
Ile105Val or RRM1 C37A-T524C, the joint detection of both may be more helpful for
NSCLC patients to accept gemcitabine-cisplatin regimens as first-line chemotherapy.
Especially, genetic polymorphism of RRM1 is more likely to be used as an important
biomarker to predict response and toxicity to gemcitabine-cisplatin combination
chemotherapy in NSCLC.