Potentially functional genetic variants in the complement-related immunity gene-set are associated with non-small cell lung cancer survival

Details

• Alternative Title:
  Int J Cancer
• Personal Author:
  Qian, Danwen ; Liu, Hongliang ; Wang, Xiaomeng ; Ge, Jie ; Luo, Sheng ; Patz, Edward F. ; Moorman, Patricia G. ; Su, Li ; Shen, Sipeng ; Christiani, David C. ; Wei, Qingyi
• 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| ), 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.
• Subjects:
  Adult Carcinoma, Non-Small-Cell Lung Complement Activation Complement System Proteins Datasets As Topic Female Follow-Up Studies Genome-Wide Association Study Humans Lung Neoplasms Male Polymorphism, Single Nucleotide Quantitative Trait Loci Survival Analysis Tumor Microenvironment Von Willebrand Factor Young Adult

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• Keywords:
  Complement Pathway Genome-wide Association Study Non-small Cell Lung Cancer Overall Survival Single-nucleotide Polymorphism
• Source:
  Int J Cancer. 144(8):1867-1876
• Pubmed ID:
  30259978
• Pubmed Central ID:
  PMC6377316
• Document Type:
  Journal Article
• Funding:
  P20 CA090578/CA/NCI NIH HHSUnited States/ ; R01 NS091307/NS/NINDS NIH HHSUnited States/ ; R01 CA092824/CA/NCI NIH HHSUnited States/ ; R35 CA197449/CA/NCI NIH HHSUnited States/ ; T42 OH008416/OH/NIOSH CDC HHSUnited States/ ; R01 CA074386/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/
• Volume:
  144
• Issue:
  8
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:b0758d2e32a6fb4989885eceec0cd4664c89c7cf6aca1b2dbd4e145e6b4436ee
• Download URL:
  https://stacks.cdc.gov/view/cdc/76915/cdc_76915_DS1.pdf
• File Type:
  [PDF - 949.76 KB ]