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

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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

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MicroRNAs
Non-Small Cell Lung Carcinoma
Confidence Intervals
Single Nucleotide Polymorphism
Alleles
Binding Sites
Recurrence
Survival
Human Genome
Survival Analysis
Luciferases
Nucleotides
Genotype
Population
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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MicroRNA-related genetic variants associated with clinical outcomes in early-stage non-small cell lung cancer patients. / Pu, Xia; Roth, Jack A.; Hildebrandt, Michelle A T; Ye, Yuanqing; Wei, Hua; Minna, John D.; Lippman, Scott M.; Wu, Xifeng.

In: Cancer Research, Vol. 73, No. 6, 15.03.2013, p. 1867-1875.

Research output: Contribution to journalArticle

Pu, Xia ; Roth, Jack A. ; Hildebrandt, Michelle A T ; Ye, Yuanqing ; Wei, Hua ; Minna, John D. ; Lippman, Scott M. ; Wu, Xifeng. / MicroRNA-related genetic variants associated with clinical outcomes in early-stage non-small cell lung cancer patients. In: Cancer Research. 2013 ; Vol. 73, No. 6. pp. 1867-1875.
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