Potentially Functional Genetic Variants in the Complement-Related Immunity Gene-Set Are Associated with Non-Small Cell Lung Cancer Survival

Details

• Personal Author:
  Christiani, David C. ; Ge J ; Liu H ; Luo S ; Moorman PG ; Patz EF Jr. ; Qian D ; Shen S ; Su L ; Wang X ; Wei Q
• Description:
  The complement system plays an important role in the innate and adaptive immunity, complement components mediate tumor cytolysis of antibody-based immunotherapy, and complement activation in the tumor microenvironment may promote tumor progression or inhibition, depending on the mechanism of action. In the present study, we conducted a two-phase analysis of two independently published genome-wide association studies (GWASs) for associations between genetic variants in a complement-related immunity gene-set and overall survival of non-small cell lung cancer (NSCLC). The GWAS dataset from Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was used as the discovery, and multivariate Cox proportional hazards regression with false-positive report probability for multiple test corrections were performed to evaluate associations between 14,699 single-nucleotide polymorphisms (SNPs) in 111 genes and survival of 1,185 NSCLC patients. The identified significant SNPs in a single-locus analysis were further validated with 984 NSCLC patients in the GWAS dataset from the Harvard Lung Cancer Susceptibility (HLCS) Study. The results showed that two independent, potentially functional SNPs in two genes (VWF rs73049469 and ITGB2 rs3788142) were significantly associated with NSCLC survival, with a combined hazards ratio (HR) of 1.22 [95% confidence interval (CI) = 1.07-1.40, P = 0.002] and 1.16 (1.07-1.27, 6.45 × 10-4), respectively. Finally, we performed expression quantitative trait loci (eQTL) analysis and found that survival-associated genotypes of VWF rs73049469 were also significantly associated with mRNA expression levels of the gene. These results indicated that genetic variants of the complement-related immunity genes might be predictors of NSCLC survival, particularly for the short-term survival, possibly by modulating the expression of genes involved in the host immunity. [Description provided by NIOSH]
• Subjects:
  Genetics Immune System Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: Non-small Cell Lung Cancer Cell Function Complement Pathway Genes Genetic Factors Genome-wide Association Study Immune System Lung Cancer Overall Survival Single-nucleotide Polymorphism
• ISSN:
  0020-7136
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; North Carolina ; OSHA Region 1 ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  144
• Issue:
  8
• NIOSHTIC Number:
  nn:20055708
• Citation:
  Int J Cancer 2019 Apr; 144(8):1867-1876
• Contact Point Address:
  Qingyi Wei, Duke Cancer Institute, Duke University Medical Center and Department of Medicine, Duke School of Medicine, 905 S LaSalle Street, Durham, North Carolina 27710, USA
• Email:
  qingyi.wei@duke.edu
• Federal Fiscal Year:
  2019
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20050701
• 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:be4391f066ea22f5efea9093b2247aa3959e0ca143a4561377f94962ed78fb99285a5035915c025c09270bd51bf7fd1ae48c0a0fbe01c7a25554820db07da892
• Download URL:
  https://stacks.cdc.gov/view/cdc/213496/cdc_213496_DS1.pdf
• File Type:
  [PDF - 640.33 KB ]