Correlations between microsatellite instability, ERCC1/XRCC1 polymorphism and clinical characteristics, and FOLFOX adjuvant chemotherapy effect of colorectal cancer patients

Cancer Genet. 2017 Dec:218-219:51-57. doi: 10.1016/j.cancergen.2017.09.004. Epub 2017 Sep 22.

Abstract

Patients with MSI colorectal tumor have good prognosis and cannot benefit from 5-fluorouracil (5-Fu)-based chemotherapy reported by previous studies. While, single nucleotide polymorphisms (SNP) of ERCC1 and XRCC1 have be proved to influence clinical outcome of colorectal cancer patients treated with oxaliplatin-based chemotherapy. We aim to study the correlation between molecular status and clinical- pathological features, and their effect on CRC patients' clinical outcome treated with mFOLFOX6 adjuvant chemotherapy. In this study, MSI status was determined in tumors and paired normal tissues from 101 colorectal cancer (CRC) patients. We also examined SNP of ERCC1 (c. C354T) and XRCC1 (c.G1196A) in 83 and 85 patients' blood. MSI was found to be significantly correlated with well/moderate histopathological differentiation (p = 0.038) and CRC family history (p = 0.003). CEA and CA19-9 levels was positive correlated significantly by Spearman correlation analysis (Pearson's r = 0.823, p < 0.0001). No significant correlation was found between MSI status and ERCC1/XRCC1 polymorphisms. We found greater drop of CEA level in mFOLFOX6 sensitive group than low sensitive group after mFOLFOX6 adjuvant chemotherapy according to MSI status, ERCC1 and XRCC1 SNP. MSI was significantly correlated with well/moderate histopathological differentiation (p = 0.038) and CRC family history (p = 0.003). The MSI status, ERCC1 and XRCC1 polymorphisms may influence the clinical outcome of colorectal cancer patients treated with mFOLFOX6 adjuvant chemotherapy.

Keywords: ERCC1; Microsatellite instability (MSI); XRCC1; colorectal cancer; mFOLFOX6.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Female
  • Fluorouracil / therapeutic use
  • Follow-Up Studies
  • Humans
  • Leucovorin / therapeutic use
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Neoplasm Staging
  • Organoplatinum Compounds / therapeutic use
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • X-ray Repair Cross Complementing Protein 1 / genetics*

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Organoplatinum Compounds
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • ERCC1 protein, human
  • Endonucleases
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol