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

Publication ,  Journal Article
Qian, D; Liu, H; Wang, X; Ge, J; Luo, S; Patz, EF; Moorman, PG; Su, L; Shen, S; Christiani, DC; Wei, Q
Published in: Int J Cancer
April 15, 2019

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.

Duke Scholars

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

April 15, 2019

Volume

144

Issue

8

Start / End Page

1867 / 1876

Location

United States

Related Subject Headings

  • von Willebrand Factor
  • Young Adult
  • Tumor Microenvironment
  • Survival Analysis
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Male
  • Lung Neoplasms
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Qian, D., Liu, H., Wang, X., Ge, J., Luo, S., Patz, E. F., … Wei, Q. (2019). Potentially functional genetic variants in the complement-related immunity gene-set are associated with non-small cell lung cancer survival. Int J Cancer, 144(8), 1867–1876. https://doi.org/10.1002/ijc.31896
Qian, Danwen, Hongliang Liu, Xiaomeng Wang, Jie Ge, Sheng Luo, Edward F. Patz, Patricia G. Moorman, et al. “Potentially functional genetic variants in the complement-related immunity gene-set are associated with non-small cell lung cancer survival.Int J Cancer 144, no. 8 (April 15, 2019): 1867–76. https://doi.org/10.1002/ijc.31896.
Qian D, Liu H, Wang X, Ge J, Luo S, Patz EF, et al. Potentially functional genetic variants in the complement-related immunity gene-set are associated with non-small cell lung cancer survival. Int J Cancer. 2019 Apr 15;144(8):1867–76.
Qian, Danwen, et al. “Potentially functional genetic variants in the complement-related immunity gene-set are associated with non-small cell lung cancer survival.Int J Cancer, vol. 144, no. 8, Apr. 2019, pp. 1867–76. Pubmed, doi:10.1002/ijc.31896.
Qian D, Liu H, Wang X, Ge J, Luo S, Patz EF, Moorman PG, Su L, Shen S, Christiani DC, Wei Q. Potentially functional genetic variants in the complement-related immunity gene-set are associated with non-small cell lung cancer survival. Int J Cancer. 2019 Apr 15;144(8):1867–1876.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

April 15, 2019

Volume

144

Issue

8

Start / End Page

1867 / 1876

Location

United States

Related Subject Headings

  • von Willebrand Factor
  • Young Adult
  • Tumor Microenvironment
  • Survival Analysis
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Male
  • Lung Neoplasms
  • Humans