Associations between oxaliplatin-induced peripheral neuropathy and polymorphisms of the ERCC1 and GSTP1 genes.
OBJECTIVE
Oxaliplatin-induced chronic neuropathy is cumulative and dose-limiting; reliable predictors and determination of the mechanism of this toxic effect are needed.


METHODS
We retrospectively studied 51 Japanese adults with colorectal cancer who had received oxaliplatin-based chemotherapy to explore the pharmacogenetic association between oxaliplatin-induced neuropathy and polymorphisms of the excision repair cross-complementation Group 1 (ERCC1) and glutathione-S-transferases pi 1 (GSTP1) genes.


RESULTS
For the ERCC1 C118T polymorphism, Grade 1 chronic neuropathy developed earlier in patients with C/T and T/T genotypes (median number of treatment cycles at onset = 6) than in those with the reference C/C genotype (7 cycles; p = 0.0162 by the generalized Wilcoxon test). For the GSTP1 Ile105Val polymorphism, chronic neuropathy developed earlier in patients with the reference Ile/Ile genotype (6 cycles) than in those with Ile/Val and Val/Val genotypes (9 cycles; p = 0.0321). ERCC1 C118T and GSTP1 Ile105Val polymorphisms were not significantly associated with an increased risk of developing Grade 2 or more severe chronic neuropathy.


CONCLUSIONS
Our results suggest that ERCC1, C118T and GSTP1 Ile105Val polymorphisms are more strongly related to the time until onset of neuropathy than to the grade of neuropathy. Most likely these polymorphisms influence patients' sensitivity to neuropathy.
Inada
M
M
Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan. m-inada@med.nagoya-u.ac.jp
Sato
M
M
Morita
S
S
Kitagawa
K
K
Kawada
K
K
Mitsuma
A
A
Sawaki
M
M
Fujita
K
K
Ando
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D044466:Asian People / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D007564:Japan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D013997:Time Factors
D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; C071447:ERCC1 protein, human; D004720:Endonucleases; D002955:Leucovorin; D005472:Fluorouracil