Published in:
01-06-2013 | Original Article
Differential toxicity biomarkers for irinotecan- and oxaliplatin-containing chemotherapy in colorectal cancer
Authors:
Lucía Cortejoso, María I. García, Pilar García-Alfonso, Eva González-Haba, Fernando Escolar, María Sanjurjo, Luis A. López-Fernández
Published in:
Cancer Chemotherapy and Pharmacology
|
Issue 6/2013
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Abstract
Purpose
Oxaliplatin or irinotecan is usually administered jointly with fluoropyrimidines in colorectal cancer patients treated with chemotherapy. Both drugs have different toxicity patterns. Biomarkers for predicting high-risk severe adverse reactions can help select the best treatment.
Methods
A retrospective analysis of 106 colorectal cancer patients receiving an oxaliplatin-based treatment and 56 receiving an irinotecan-based treatment was performed. One copy number variant (GSTT1) and nine polymorphisms in irinotecan and oxaliplatin metabolism, transport or DNA repair genes (ABCB1, UGT1A1, XRCC1, ERCC1, ERCC2, GSTP1) were genotyped by SNaPshot, polymerase chain reactions’ length fragments, or copy number assays.
Results
In irinotecan-treated patients, C allele of ABCB1 C1236T SNP was associated with a lower risk of asthenia (OR = 0.043; 96 % CI = 0.004–0.444; P = 0.008) and C allele of ABCB1 C3435T SNP was associated with a lower risk of diarrhea (OR = 0.162; 95 % CI = 0.031–0.844; P = 0.031); and individuals with two copies of GSTT1 gene had a lower risk for asthenia (OR = 0.074; 95 % CI = 0.009–0.617; P = 0.016). In oxaliplatin-treated patients, carriers of two C variants of Asn118Asn ERCC1 SNP had a lower risk for neutropenia (OR = 0.203; 95 % CI = 0.060–0.683; P = 0.01).
Conclusions
These biomarkers could help oncologists select the best treatment by reducing toxicity associated with irinotecan or oxaliplatin in colorectal cancer patients, thus increasing their quality of life.