Very low prevalence of XPD K751Q polymorphism and its association with XPD expression and outcomes of FOLFOX-4 treatment in Asian patients with colorectal carcinoma

Cancer Sci. 2009 Jul;100(7):1261-6. doi: 10.1111/j.1349-7006.2009.01186.x. Epub 2009 May 4.

Abstract

Xeroderma pigmentosum group D (XPD) participates in DNA unwinding during nucleotide excision repair, which may alter the efficacy of platinum-based chemotherapy. We analyzed the influence of codon 751 Lys-->Gln polymorphism of XPD on its protein expression levels, clinico-pathological features, and outcome of 188 Chinese patients with metastatic colorectal carcinoma (CRC) that had been treated with first-line Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX-4) chemotherapy. The results showed that in comparison with Caucasian populations, a remarkably lower prevalence of Lys/Gln genotype was noted (16%, n = 30). No between-group difference in XPD protein expression of patients with or without this polymorphism was noted (56.5%vs 59.7%; P = 0.783). Patients with Gln751 allele have a significantly lower response to FOLFOX-4 treatment (36.7%vs 58.2%, P = 0.03), and shorter progression-free (7 vs 11 months; P < 0.01) and overall (14 vs 22 months; P < 0.01) survivals. The incidence of grade 3/4 oxaliplatin-neuropathies was very similar in both groups (13.3%vs 16.5%; P = 0.67). By adjusted analysis, this polymorphism was further identified as an independent prognostic factor (P = 0.03). These data suggest that Asian populations have a significantly lower prevalence of codon 751 Lys/Gln polymorphism in XPD, which could be a key determinant for good response to oxaliplatin-based treatment and favorable outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asian Continental Ancestry Group / genetics
  • Carcinoma / drug therapy*
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / therapeutic use
  • Polymorphism, Genetic*
  • Prevalence
  • Xeroderma Pigmentosum Group D Protein / genetics*

Substances

  • Organoplatinum Compounds
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol