Influence of the KDM4A rs586339 polymorphism on overall survival in Asian non-small-cell lung cancer patients

Pharmacogenet Genomics. 2017 Mar;27(3):120-123. doi: 10.1097/FPC.0000000000000266.

Abstract

The critical role of lysine demethylase 4A (KDM4A), in regulating chromatin structure and consequently in driving cellular proliferation and oncogenesis has been the focus of recent studies. Non-small-cell lung cancer (NSCLC) patients with adenocarcinoma histology who were homozygous for KDM4A single nucleotide polymorphism (SNP)-A482 (rs586339) were recently shown to have significantly worse overall survival (OS) compared with patients with the wild-type or the heterozygous genotype at this locus (hazard ratio=1.68, P=0.042). In the current study, we investigated the association between the same polymorphism with OS in our Asian NSCLC-adenocarcinoma patients comprising Chinese (N=572), Malays (N=50), and Indians (N=22). KDM4A SNP-A482 genotype status was determined by Sanger sequencing. OS was calculated from the date of diagnosis to date of death or censored at the date of last follow-up. Kaplan-Meier analysis, log-rank test, and Cox regression methods were utilized to evaluate OS outcomes. KDM4A SNP-A482 had a minor allele (C) frequency of 18.8% and a major allele (A) frequency of 81.2% in our Asian NSCLC (adenocarcinoma) patients. However, the OS in our Asian NSCLC patients homozygous for KDM4A SNP-A482 was not significantly different from those who were wild type or heterozygous at this locus [CC vs. AA/AC: median OS (95% confidence interval): 40.2 (18.7-61.6) vs. 29.6 (26.9-32.3) months; P=0.858]. The results remained statistically nonsignificant even after adjustment for epidermal growth factor receptor mutational status, suggesting that KDM4A SNP-A482 does not significantly influence OS in Asian NSCLC patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People / ethnology*
  • Asian People / genetics
  • Carcinoma, Non-Small-Cell Lung / ethnology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Female
  • Genetic Association Studies
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics*
  • Kaplan-Meier Estimate
  • Lung Neoplasms / ethnology
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Sequence Analysis, DNA
  • Survival Analysis

Substances

  • Jumonji Domain-Containing Histone Demethylases
  • KDM4A protein, human