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

Details

• Alternative Title:
  Int J Cancer
• Personal Author:
  Xu, Yinghui ; Liu, Hongliang ; Liu, Shun ; Wang, Yanru ; Xie, Jichun ; Stinchcombe, Thomas E. ; Su, Li ; Zhang, Ruyang ; Christiani, David C. ; Li, Wei ; Wei, Qingyi
• Description:
  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| ) 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.
• Subjects:
  Aged Carcinoma, Non-Small-Cell Lung Female Genetic Variation Genome-Wide Association Study Humans Interleukin-1 Receptor-Associated Kinases Lung Neoplasms Male Middle Aged Multicenter Studies As Topic Polymorphism, Single Nucleotide Proportional Hazards Models Randomized Controlled Trials As Topic RNA, Messenger Signal Transduction Survival Analysis Toll-Like Receptors United States

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• Keywords:
  Genome-wide Association Study (GWAS) Non-small Cell Lung Cancer (NSCLC) Overall Survival (OS) Single-nucleotide Polymorphism (SNP) Toll-like Receptor (TLR)
• Source:
  Int J Cancer. 143(10):2400-2408
• Pubmed ID:
  29978465
• Pubmed Central ID:
  PMC6205899
• Document Type:
  Journal Article
• Funding:
  P20 CA090578/CA/NCI NIH HHSUnited States/ ; T42 OH008416/OH/NIOSH CDC HHSUnited States/ ; R01 CA074386/CA/NCI NIH HHSUnited States/ ; P30 CA021765/CA/NCI NIH HHSUnited States/ ; P50 CA090578/CA/NCI NIH HHSUnited States/ ; P30 CA014236/CA/NCI NIH HHSUnited States/ ; U01 CA209414/CA/NCI NIH HHSUnited States/ ; R01 CA092824/CA/NCI NIH HHSUnited States/ ; R35 CA197449/CA/NCI NIH HHSUnited States/
• Volume:
  143
• Issue:
  10
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:fd775595a4e80b456d83932f15f29e8a2124572d0027f4c30c991c8a22fc5bac
• Download URL:
  https://stacks.cdc.gov/view/cdc/76898/cdc_76898_DS1.pdf
• File Type:
  [PDF - 524.78 KB ]