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

Int J Cancer. 2018 Nov 15;143(10):2400-2408. doi: 10.1002/ijc.31660. Epub 2018 Sep 21.


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.

Keywords: Non-small cell lung cancer; genome-wide association study; overall survival; single-nucleotide polymorphism; toll-like receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Female
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans
  • Interleukin-1 Receptor-Associated Kinases / genetics*
  • Interleukin-1 Receptor-Associated Kinases / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality*
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Polymorphism, Single Nucleotide
  • Proportional Hazards Models
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Randomized Controlled Trials as Topic
  • Signal Transduction / genetics
  • Survival Analysis
  • Toll-Like Receptors / genetics*
  • Toll-Like Receptors / metabolism
  • United States / epidemiology


  • RNA, Messenger
  • Toll-Like Receptors
  • Interleukin-1 Receptor-Associated Kinases