Skip to Main Content

An official website of the United States government

Government Funding Lapse

Because of a lapse in government funding, the information on this website may not be up to date, transactions submitted via the website may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted. The NIH Clinical Center (the research hospital of NIH) is open. For more details about its operating status, please visit  cc.nih.gov. Updates regarding government operating status and resumption of normal operations can be found at OPM.gov.

Genetic variants of BIRC3 and NRG1 in the NLRP3 inflammasome pathway are associated with non-small cell lung cancer survival.

About this Publication
Title
Genetic variants of BIRC3 and NRG1 in the NLRP3 inflammasome pathway are associated with non-small cell lung cancer survival.
Pubmed ID
32905523 (View this publication on the PubMed website)
Publication
Am J Cancer Res. 2020; Volume 10 (Issue 8): Pages 2582-2595
Authors
Tang D, Liu H, Zhao Y, Qian D, Luo S, Patz EF, Su L, Shen S, ChristianI DC, Gao W, Wei Q
Affiliations
  • Department of Thoracic Oncology, Huadong Hospital Affiliated to Fudan University Shanghai 200040, China.
  • Duke Cancer Institute, Duke University Medical Center Durham, NC 27710, USA.
  • Department of Biostatistics and Bioinformatics, Duke University School of Medicine Durham, NC 27710, USA.
  • Department of Environmental Health and Department of Epidemiology, Harvard School of Public Health Boston, MA 02115, USA.
Abstract

The nod-like receptor protein 3 (NLRP3) is one of the most characterized inflammasomes, and its genetic variation and functional dysregulation are involved in pathogenesis of several cancers. To systematically evaluate the role of NLRP3 in predicting outcomes of patients with non-small cell lung cancer (NSCLC), we performed a two-phase analysis for associations between genetic variants in NLRP3 inflammasome pathway genes and NSCLC survival by using a published genome-wide association study (GWAS) dataset from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. We used multivariate Cox proportional hazards regression analysis with Bayesian false discovery probability (≤0.80) for multiple testing correction to evaluate associations between 20,730 single-nucleotide polymorphisms (SNPs) in 176 genes and overall survival of 1,185 NSCLC patients from the PLCO trial. We further validated the identified significant SNPs in another GWAS dataset with survival data from 984 NSCLC patients of the Harvard Lung Cancer Susceptibility (HLCS) study. The results showed that two independent SNPs in two different genes (i.e., BIRC3 rs11225211 and NRG1 rs4733124) were significantly associated with the NSCLC overall survival, with a combined hazards ratio (HR) of 0.83 [95% confidence interval (CI) = 0.74-0.93 and P = 0.0009] and 1.18 (95% CI = 1.06-1.31) and P = 0.002], respectively. However, further expression quantitative trait loci (eQTL) analysis showed no evidence for correlations between the two SNPs and mRNA expression levels of corresponding genes. These results indicated that genetic variants in the NLRP3 imflammasome pathway gene-sets might be predictors of NSCLC survival, but the molecular mechanisms underlying the observed associations warrant further investigations.

Related CDAS Studies
Related CDAS Projects