Pharmacogenetic analysis of adjuvant FOLFOX for Korean patients with colon cancer

Cancer Chemother Pharmacol. 2013 Apr;71(4):843-51. doi: 10.1007/s00280-013-2075-3. Epub 2013 Jan 13.

Abstract

Purpose: Ethnic diversity of genetic polymorphism can result in individual differences in the efficacy and toxicity of cancer chemotherapy.

Methods: We analyzed 20 germline polymorphisms in 10 genes (TS, MTHFR, ERCC1, XPD, XRCC1, ABCC2, AGXT, GSTP1, GSTT1 and GSTM1) from prospectively enrolled 292 Korean patients treated with adjuvant oxaliplatin plus leucovorin plus 5-fluorouracil (FOLFOX) for colon cancer.

Results: In contrast to previous studies in Caucasians, neutropenia (grade 3-4, 60.5 %) was frequently observed, whereas only 16.4 % experienced grade 2 or more sensory neuropathy. Neutropenia was more frequent in MTHFR 677TT [adjusted odds ratio (OR) 2.32, 95 % confidence interval (CI) 1.19-4.55] and ERCC1 19007TT (adjusted OR 4.58, 95 % CI 1.20-17.40) genotypes. Patients harboring XRCC1 23885GG experienced less grade 2-4 neuropathy [adjusted OR 0.52, 95 % CI 0.27-0.99]. MTHFR 677TT (p = 0.002) and XRCC1 23885GG (p = 0.146) genotypes were also more prevalent in Koreans compared to Caucasians. TS 'low' genotype (adjusted HR 1.83, 95 % CI 1.003-3.34) was significantly related to shorter disease-free survival. Overall survival was not significantly different according to the polymorphisms.

Conclusions: Polymorphisms in MTHFR, XRCC1 and TS are related to toxicities and disease-free survival in patients with colon cancer. The ethnic differences in frequencies of genotypes may explain the ethnic difference in toxicity profile following adjuvant FOLFOX chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / mortality
  • DNA-Binding Proteins / genetics
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Genotype
  • Humans
  • Korea
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide
  • Proportional Hazards Models
  • X-ray Repair Cross Complementing Protein 1

Substances

  • DNA-Binding Proteins
  • Organoplatinum Compounds
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol