Genetic variant of IRAK2 in the toll-like receptor signaling pathway and survival of non-small cell lung cancer.
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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.
Carcinoma, Non-Small-Cell Lung
Proportional Hazards Models
Polymorphism, Single Nucleotide
Interleukin-1 Receptor-Associated Kinases
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
Genome-Wide Association Study
Published Version (Please cite this version)10.1002/ijc.31660
Publication InfoXu, Yinghui; Liu, Hongliang; Liu, Shun; Wang, Yanru; Xie, Jichun; Stinchcombe, Thomas E; ... Wei, Qingyi (2018). Genetic variant of IRAK2 in the toll-like receptor signaling pathway and survival of non-small cell lung cancer. International journal of cancer, 143(10). pp. 2400-2408. 10.1002/ijc.31660. Retrieved from https://hdl.handle.net/10161/18500.
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Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally recognized epidemiologist focused on the molecular and genetic epidemiology of head and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and genetic determinants for the DNA repair deficient phenotype and
Associate Professor of Biostatistics & Bioinformatics
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