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Polymorphisms of GSTP1, ERCC2 and TS‑3'UTR are associated with the clinical outcome of mFOLFOX6 in colorectal cancer patients

  • Authors:
    • Kensuke Kumamoto
    • Keiichiro Ishibashi
    • Norimichi Okada
    • Yusuke Tajima
    • Kouki Kuwabara
    • Yoichi Kumagai
    • Hiroyuki Baba
    • Norihiro Haga
    • Hideyuki Ishida

  • View Affiliations

  • Published online on: July 15, 2013     https://doi.org/10.3892/ol.2013.1467
  • Pages: 648-654
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Abstract

The aim of the current study was to examine whether polymorphisms in drug metabolism genes have any clinical impact on patients treated with 5‑fluorouracil (FU)/oxaliplatin for metastatic colorectal cancer (MCRC). In total, 63 patients with MCRC were recruited and treated with a modified FOLFOX6 (mFOLFOX6) treatment as a first‑line chemotherapy. Polymorphisms in five drug metabolism genes and two DNA‑repair genes were assessed in these patients using polymerase chain reaction (PCR), a PCR restriction fragment length polymorphism (PCR‑RFLP) technique or invader techniques. These included a 28‑bp tandem repeat in the 5'‑untranslated region (UTR) and 6‑bp deletions in the 3'‑UTR of thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR; Ala677Val), glutathione S‑transferase π (GSTP1; IIe105Val), GST θ1 (GSTT1; deletion) and GST µ1 (GSTM1; deletion) and the two DNA‑repair genes, excision repair cross‑complementing‑1 (ERCC1; Asp118Asn) and ERCC2 (Lys751Gln). The correlation between these polymorphisms and the clinical outcome, including drug response, progression‑free survival (PFS), overall survival (OS) and the incidence of peripheral neuropathy, were evaluated. Patients with the GSTP1‑105 A/A genotype had poor responses to mFOLFOX6 treatment compared with those with the GSTP1‑105 A/G and G/G genotypes (P=0.01). The median PFS of patients with the ERCC2‑751 A/A genotype tended to be longer than that of patients with the ERCC2‑751 A/C genotype (P=0.05). Patients with the TS‑3'‑UTR ‑6/‑6 genotype had a significantly longer OS compared with patients with other genotypes (P=0.003). A statistically significant association between the incidence of peripheral neuropathy higher than grade 2 and the GSTP1‑105 (P=0.03) and GSTM1 genotypes (P=0.02) was identified by multivariate logistic regression analyses. Results demonstrated that polymorphisms in GSTP1‑105, ERCC2‑751 and the 3'‑UTR of TS may be a statistically significant predictors of clinical outcome. GSTP1‑105 and GSTM1 genotypes may be useful markers of severe peripheral neuropathy in MCRC patients treated with 5‑FU/oxaliplatin as first‑line chemotherapy.
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September 2013
Volume 6 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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  • Journal Metrics
  • Impact Factor: 2.9
  • Ranked Oncology
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  • CiteScore: 6.3
  • CiteScore Rank: Q2: #119/366 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.725
  • SCImago Journal Rank (SJR): 0.639
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Spandidos Publications style
Kumamoto K, Ishibashi K, Okada N, Tajima Y, Kuwabara K, Kumagai Y, Baba H, Haga N and Ishida H: Polymorphisms of GSTP1, ERCC2 and TS‑3'UTR are associated with the clinical outcome of mFOLFOX6 in colorectal cancer patients. Oncol Lett 6: 648-654, 2013
APA
Kumamoto, K., Ishibashi, K., Okada, N., Tajima, Y., Kuwabara, K., Kumagai, Y. ... Ishida, H. (2013). Polymorphisms of GSTP1, ERCC2 and TS‑3'UTR are associated with the clinical outcome of mFOLFOX6 in colorectal cancer patients. Oncology Letters, 6, 648-654. https://doi.org/10.3892/ol.2013.1467
MLA
Kumamoto, K., Ishibashi, K., Okada, N., Tajima, Y., Kuwabara, K., Kumagai, Y., Baba, H., Haga, N., Ishida, H."Polymorphisms of GSTP1, ERCC2 and TS‑3'UTR are associated with the clinical outcome of mFOLFOX6 in colorectal cancer patients". Oncology Letters 6.3 (2013): 648-654.
Chicago
Kumamoto, K., Ishibashi, K., Okada, N., Tajima, Y., Kuwabara, K., Kumagai, Y., Baba, H., Haga, N., Ishida, H."Polymorphisms of GSTP1, ERCC2 and TS‑3'UTR are associated with the clinical outcome of mFOLFOX6 in colorectal cancer patients". Oncology Letters 6, no. 3 (2013): 648-654. https://doi.org/10.3892/ol.2013.1467