MicroRNA-related genetic variants associated with clinical outcomes in early-stage non-small cell lung cancer patients

Xia Pu, Jack A. Roth, Michelle A T Hildebrandt, Yuanqing Ye, Hua Wei, John D. Minna, Scott M. Lippman, Xifeng Wu

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Given the density of single-nucleotide polymorphisms (SNP) in the human genome and the sensitivity of single-nucleotide changes in microRNA (miRNA) functionality and processing, we asked whether polymorphisms within miRNA processing pathways and binding sites may influence non-small cell lung cancer (NSCLC) patients' prognosis. We genotyped 240 miRNA-related SNPs in 535 patients with stage I and II NSCLCs to determine associations with overall recurrence and survival as well as effect in specific treatment subgroups. After correcting for multiple comparisons, the G allele of FZD4:rs713065 displayed a significant association with decreased risk of death in surgery-only patients [HR, 0.46; 95% confidence interval (CI), 0.32-0.65]. DROSHA:rs6886834 variant A allele (HR, 6.38; 95% CI, 2.49-16.31) remained significant for increased risk of recurrence in the overall and surgeryonly populations, respectively. FAS:rs2234978 G allele remained significantly associated with survival in all patients (HR, 0.59; 95% CI, 0.44-0.77), whereas borderline significant in subgroups (surgery-only: HR, 0.59; 95% CI, 0.42-0.84; surgery plus chemo: HR, 0.19; 95% CI, 0.07-0.46). Luciferase assays showed that the FAS SNP created a miR-651 functional binding site. Survival tree analysis was conducted to classify patients into distinct risk subgroups based on their risk genotype combinations. These results indicate that miRNA-related polymorphisms may be associated with NSCLC patients' clinical outcomes through altered miRNA regulation of target genes.

Original languageEnglish (US)
Pages (from-to)1867-1875
Number of pages9
JournalCancer research
Volume73
Issue number6
DOIs
StatePublished - Mar 15 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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