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Functional variants in DCAF4 associated with lung cancer risk in European populations.

Publication ,  Journal Article
Liu, H; Liu, Z; Wang, Y; Stinchcombe, TE; Owzar, K; Han, Y; Hung, RJ; Brhane, Y; McLaughlin, J; Brennan, P; Bickeböller, H; Rosenberger, A ...
Published in: Carcinogenesis
May 1, 2017

Cullin-RING ubiquitin ligases (CRLs) responsible for substrate specificity of ubiquitination play a key role in cell-cycle control and DNA damage response. In this study, we assessed associations between 16 599 SNPs in 115 CRL genes and lung cancer risk by using summary data of six published genome-wide association studies (GWASs) of 12 160 cases and 16 838 cases of European ancestry. As a result, we identified three independent SNPs in DCAF4 (rs117781739, rs12587742 and rs2240980) associated with lung cancer risk (odds ratio = 0.91, 1.09 and 1.09, respectively; 95% confidence interval = 0.88-0.95, 1.05-1.14 and 1.05-1.13, respectively; and P = 3.99 × 10-6, 4.97 × 10-5 and 1.44 × 10-5, respectively) after multiple comparison correction by a false discovery rate <0.05. Since SNP rs12587742 is located within the promoter region and one CpG island of DCAF4, we further performed in silico functional analyses and found that the rs12587742 variant A allele was associated with an increased mRNA expression (P = 2.20 × 10-16, 1.79 × 10-13 and 0.001 in blood cells, normal lung tissues and tumor tissues of lung squamous carcinoma, respectively) and a decreased methylation status (P = 2.48 × 10-9 and 0.032 in adipose and lung tumor tissues, respectively). Moreover, evidence from differential expression analyses further supported an oncogenic effect of DCAF4 on lung cancer, with higher mRNA levels in both lung squamous carcinoma and adenocarcinoma (P = 4.48 × 10-11 and 1.22 × 10-9, respectively) than in adjacent normal tissues. Taken together, our results suggest that rs12587742 is associated with an increased lung cancer risk, possibly by up-regulating mRNA expression and decreasing methylation status of DCAF4.

Duke Scholars

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

May 1, 2017

Volume

38

Issue

5

Start / End Page

541 / 551

Location

England

Related Subject Headings

  • White People
  • Risk Factors
  • Risk
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Odds Ratio
  • Lung Neoplasms
  • Linkage Disequilibrium
  • Humans
  • Genome-Wide Association Study
 

Citation

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Liu, H., Liu, Z., Wang, Y., Stinchcombe, T. E., Owzar, K., Han, Y., … Transdisciplinary Research in Cancer of the Lung (TRICL) Research Team, . (2017). Functional variants in DCAF4 associated with lung cancer risk in European populations. Carcinogenesis, 38(5), 541–551. https://doi.org/10.1093/carcin/bgx033
Liu, Hongliang, Zhensheng Liu, Yanru Wang, Thomas E. Stinchcombe, Kouros Owzar, Younghun Han, Rayjean J. Hung, et al. “Functional variants in DCAF4 associated with lung cancer risk in European populations.Carcinogenesis 38, no. 5 (May 1, 2017): 541–51. https://doi.org/10.1093/carcin/bgx033.
Liu H, Liu Z, Wang Y, Stinchcombe TE, Owzar K, Han Y, et al. Functional variants in DCAF4 associated with lung cancer risk in European populations. Carcinogenesis. 2017 May 1;38(5):541–51.
Liu, Hongliang, et al. “Functional variants in DCAF4 associated with lung cancer risk in European populations.Carcinogenesis, vol. 38, no. 5, May 2017, pp. 541–51. Pubmed, doi:10.1093/carcin/bgx033.
Liu H, Liu Z, Wang Y, Stinchcombe TE, Owzar K, Han Y, Hung RJ, Brhane Y, McLaughlin J, Brennan P, Bickeböller H, Rosenberger A, Houlston RS, Caporaso N, Landi MT, Brüske I, Risch A, Wu X, Ye Y, Christiani DC, Amos CI, Wei Q, Transdisciplinary Research in Cancer of the Lung (TRICL) Research Team. Functional variants in DCAF4 associated with lung cancer risk in European populations. Carcinogenesis. 2017 May 1;38(5):541–551.
Journal cover image

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

May 1, 2017

Volume

38

Issue

5

Start / End Page

541 / 551

Location

England

Related Subject Headings

  • White People
  • Risk Factors
  • Risk
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Odds Ratio
  • Lung Neoplasms
  • Linkage Disequilibrium
  • Humans
  • Genome-Wide Association Study