GALNT14 Genotype Predicts Postoperative Outcome of Stage III Colorectal Cancer With Oxaliplatin as Adjuvant Chemotherapy

Medicine (Baltimore). 2016 Apr;95(17):e3487. doi: 10.1097/MD.0000000000003487.

Abstract

Adjuvant oxaliplatin-based chemotherapy is widely used for stage III colorectal cancer (CRC) after curative surgery. CRC is a molecularly heterogeneous disease, and our current knowledge of therapeutic response-related genetic factors remains limited. N-acetylgalactosaminyltransferase 14 (GALNT14)-rs9679162 genotype is a prognostic predictor for chemotherapy response in advanced hepatocellular carcinoma. Here, we investigated whether this genotype was related to the therapeutic outcome of stage III CRC.A cohort of 300 stage III CRC patients receiving curative resection followed by oxaliplatin-based chemotherapy was retrospectively recruited. GALNT14 genotypes and the clinicopathological factors were correlated with posttherapeutic prognosis.Of these patients, 18% patients had GALNT14-rs9679162 "TT" and 82% had the "GT" + "GG" genotypes. The analysis showed that the "TT" genotype was associated with unfavorable overall survival (OS, P = 0.009) but not with recurrence-free survival (RFS, P = 0.700). The subgroup analysis showed that the "TT" genotype was associated with unfavorable OS in the following subgroups: age ≤65 years, men, left side CRC, N2 stage, carcinoembryonic antigen >5 ng/mL, and mucinous histology (P = 0.012, 0.011, 0.009, 0.025, 0.013, and 0.007, respectively). Within the latter 2 subgroups, the "TT" genotype was the only independent predictor for OS. Finally, the "TT" genotype was associated with the T4 tumor stage (P = 0.017) and in patients with T4 tumors, the "TT" genotype was the only independent predictor for unfavorable RFS (P = 0.007).GALNT14 "TT" genotype was associated with unfavorable OS in stage III CRC patients receiving curative surgery and adjuvant oxaliplatin-based chemotherapy.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Capecitabine
  • Chemotherapy, Adjuvant*
  • Cohort Studies
  • Colectomy*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • Combined Modality Therapy
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives*
  • Genotype*
  • Humans
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • N-Acetylgalactosaminyltransferases / genetics*
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage*
  • Oxaliplatin
  • Oxaloacetates
  • Predictive Value of Tests
  • Prognosis
  • Retrospective Studies
  • Survival Analysis

Substances

  • Organoplatinum Compounds
  • Oxaloacetates
  • Oxaliplatin
  • Deoxycytidine
  • Capecitabine
  • N-Acetylgalactosaminyltransferases
  • UDP-N-acetyl-D-galactosamine polypeptide N-acetylgalactosaminyltransferase 14, human
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol
  • XELOX