Genetic variants of genes in the Notch signaling pathway predict overall survival of non-small cell lung cancer patients in the PLCO study.

Journal Article (Journal Article)

The Notch signaling pathway has been shown to have biological significance and therapeutic application in non-small cell lung cancer (NSCLC). We hypothesize that genetic variants of genes in the Notch signaling pathway are associated with overall survival (OS) of NSCLC patients. To test this hypothesis, we performed multivariate Cox proportional hazards regression analysis to evaluate associations of 19,571 single nucleotide polymorphisms (SNPs) in 132 Notch pathway genes with OS of 1,185 NSCLC patients available from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. We found that five potentially functional tagSNPs in four genes (i.e., ADAM12 rs10794069 A > G, DTX1 rs1732793 G > A, TLE1 rs199731120 C > CA, TLE1 rs35970494 T > TC and E2F3 rs3806116 G > T) were associated with a poor OS, with a variant-allele attributed hazards ratio (HR) of 1.27 [95% confidence interval (95% CI) = 1.13-1.42, P = 3.62E-05], 1.30 (1.14-1.49, 8.16E-05), 1.40 (1.16-1.68, 3.47E-04), 1.27 (1.11-1.44, 3.38E-04), and 1.21 (1.09-1.33, 2.56E-04), respectively. Combined analysis of these five risk genotypes revealed that the genetic score 0-5 was associated with the adjusted HR in a dose-response manner (Ptrend = 3.44E-13); individuals with 2-5 risk genotypes had an adjusted HR of 1.56 (1.34-1.82, 1.46E-08), compared with those with 0-1 risk genotypes. Larger studies are needed to validate our findings.

Full Text

Duke Authors

Cited Authors

  • Xu, Y; Wang, Y; Liu, H; Kang, X; Li, W; Wei, Q

Published Date

  • September 20, 2016

Published In

Volume / Issue

  • 7 / 38

Start / End Page

  • 61716 - 61727

PubMed ID

  • 27557513

Pubmed Central ID

  • PMC5308685

Electronic International Standard Serial Number (EISSN)

  • 1949-2553

Digital Object Identifier (DOI)

  • 10.18632/oncotarget.11436


  • eng

Conference Location

  • United States