Genetic Variant of IRAK2 in the Toll-Like Receptor Signaling Pathway and Survival of Non-Small Cell Lung Cancer

Details

• Personal Author:
  Christiani, David C. ; Li W ; Liu H ; Liu S ; Stinchcombe TE ; Su L ; Wang Y ; Wei Q ; Xie J ; Xu Y ; Zhang R ; Christiani, David C. ; Li W ; Liu H ; Liu S ; Stinchcombe TE ; Su L ; Wang Y ; Wei Q ; Xie J ; Xu Y ; Zhang R
• 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, 1.08x10-4 ) 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. [Description provided by NIOSH]
• Subjects:
  Antigens Biomarkers Carcinogens Genetics Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Author Keywords: Non-small Cell Lung Cancer Carcinogenesis Genome-wide Association Study Hazards Lung Cancer Lung Cells Overall Survival Single-nucleotide Polymorphism Toll-like Receptor Tumors
• ISSN:
  0020-7136
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article ; Journal Article
• Place as Subject:
  Massachusetts ; North Carolina ; OSHA Region 1 ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Volume:
  143
• Issue:
  10
• NIOSHTIC Number:
  nn:20055318
• Citation:
  Int J Cancer 2018 Nov; 143(10):2400-2408
• Contact Point Address:
  Wei Li, Cancer Center, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, China
• Email:
  jdyylw@163.com
• Federal Fiscal Year:
  2019
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20050630
• Source Full Name:
  International Journal of Cancer
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e422b89e15de7031e00dc848a2e310b182410b9e4ff24d8ce20c520b5476f7f9e32605f06878cc15ef99cc3a065dd1c82d35b4663ae7aa69e804cdf8c0f3ff17
• Download URL:
  https://stacks.cdc.gov/view/cdc/217654/cdc_217654_DS1.pdf
• File Type:
  [PDF - 439.02 KB ]