title: MicroRNA-related genetic variants associated with clinical outcomes in early-stage non-small cell lung cancer patients.
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 surgery-only 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.
authors: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Xia
authors: X
authors: Pu
authors: Jack A
authors: JA
authors: Roth
authors: Michelle A T
authors: MA
authors: Hildebrandt
authors: Yuanqing
authors: Y
authors: Ye
authors: Hua
authors: H
authors: Wei
authors: John D
authors: JD
authors: Minna
authors: Scott M
authors: SM
authors: Lippman
authors: Xifeng
authors: X
authors: Wu
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000628:therapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D035683:MicroRNAs
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