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

Publication ,  Journal Article
Xu, Y; Wang, Y; Liu, H; Kang, X; Li, W; Wei, Q
Published in: Oncotarget
September 20, 2016

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.

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Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

September 20, 2016

Volume

7

Issue

38

Start / End Page

61716 / 61727

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Signal Transduction
  • Regression Analysis
  • Registries
  • Receptors, Notch
  • Quantitative Trait Loci
  • Proportional Hazards Models
  • Polymorphism, Single Nucleotide
  • Multivariate Analysis
  • Middle Aged
 

Citation

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Xu, Y., Wang, Y., Liu, H., Kang, X., Li, W., & Wei, Q. (2016). Genetic variants of genes in the Notch signaling pathway predict overall survival of non-small cell lung cancer patients in the PLCO study. Oncotarget, 7(38), 61716–61727. https://doi.org/10.18632/oncotarget.11436
Xu, Yinghui, Yanru Wang, Hongliang Liu, Xiaozheng Kang, Wei Li, and Qingyi Wei. “Genetic variants of genes in the Notch signaling pathway predict overall survival of non-small cell lung cancer patients in the PLCO study.Oncotarget 7, no. 38 (September 20, 2016): 61716–27. https://doi.org/10.18632/oncotarget.11436.
Xu, Yinghui, et al. “Genetic variants of genes in the Notch signaling pathway predict overall survival of non-small cell lung cancer patients in the PLCO study.Oncotarget, vol. 7, no. 38, Sept. 2016, pp. 61716–27. Pubmed, doi:10.18632/oncotarget.11436.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

September 20, 2016

Volume

7

Issue

38

Start / End Page

61716 / 61727

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Signal Transduction
  • Regression Analysis
  • Registries
  • Receptors, Notch
  • Quantitative Trait Loci
  • Proportional Hazards Models
  • Polymorphism, Single Nucleotide
  • Multivariate Analysis
  • Middle Aged