Genetic variant of IRAK2 in the toll-like receptor signaling pathway and survival of non-small cell lung cancer.

Journal Article (Journal Article)

The toll-like receptor (TLR) signaling pathway plays an important role in the innate immune responses and antigen-specific acquired immunity. Aberrant activation of the TLR pathway has a significant impact on carcinogenesis or tumor progression. Therefore, we hypothesize that genetic variants in the TLR signaling pathway genes are associated with overall survival (OS) of patients with non-small cell lung cancer (NSCLC). To test this hypothesis, we first performed Cox proportional hazards regression analysis to evaluate associations between genetic variants of 165 TLR signaling pathway genes and NSCLC OS using the genome-wide association study (GWAS) dataset from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). The results were further validated by the Harvard Lung Cancer Susceptibility GWAS dataset. Specifically, we identified IRAK2 rs779901 C > T as a predictor of NSCLC OS, with a variant-allele (T) attributed hazards ratio (HR) of 0.78 [95% confidence interval (CI) = 0.67-0.91, P = 0.001] in the PLCO dataset, 0.84 (0.72-0.98, 0.031) in the Harvard dataset, and 0.81 (0.73-0.90, 1.08x10-4 ) in the meta-analysis of these two GWAS datasets. In addition, the T allele was significantly associated with an increased mRNA expression level of IRAK2. Our findings suggest that IRAK2 rs779901 C > T may be a promising prognostic biomarker for NSCLC OS.

Full Text

Duke Authors

Cited Authors

  • Xu, Y; Liu, H; Liu, S; Wang, Y; Xie, J; Stinchcombe, TE; Su, L; Zhang, R; Christiani, DC; Li, W; Wei, Q

Published Date

  • November 15, 2018

Published In

Volume / Issue

  • 143 / 10

Start / End Page

  • 2400 - 2408

PubMed ID

  • 29978465

Pubmed Central ID

  • PMC6205899

Electronic International Standard Serial Number (EISSN)

  • 1097-0215

Digital Object Identifier (DOI)

  • 10.1002/ijc.31660


  • eng

Conference Location

  • United States