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Association of a novel functional promoter variant (rs2075533 C>T) in the apoptosis gene TNFSF8 with risk of lung cancer--a finding from Texas lung cancer genome-wide association study.

Publication ,  Journal Article
Wei, S; Niu, J; Zhao, H; Liu, Z; Wang, L-E; Han, Y; Chen, WV; Amos, CI; Rafnar, T; Sulem, P; Stefansson, K; Landi, MT; Caporaso, NE; Wang, Y ...
Published in: Carcinogenesis
April 2011

Published genome-wide association studies (GWASs) have identified few variants in the known biological pathways involved in lung cancer etiology. To mine the possibly hidden causal single nucleotide polymorphisms (SNPs), we explored all SNPs in the extrinsic apoptosis pathway from our published GWAS dataset for 1154 lung cancer cases and 1137 cancer-free controls. In an initial association analysis of 611 tagSNPs in 41 apoptosis-related genes, we identified only 10 tagSNPs associated with lung cancer risk with a P value<10(-2), including four tagSNPs in DAPK1 and three tagSNPs in TNFSF8. Unlike DAPK1 SNPs, TNFSF8 rs2181033 tagged other four predicted functional but untyped SNPs (rs776576, rs776577, rs31813148 and rs2075533) in the promoter region. Therefore, we further tested binding affinity of these four SNPs by performing the electrophoretic mobility shift assay. We found that only rs2075533T allele modified levels of nuclear proteins bound to DNA, leading to significantly decreased expression of luciferase reporter constructs by 5- to -10-fold in H1299, HeLa and HCT116 cell lines compared with the C allele. We also performed a replication study of the untyped rs2075533 in an independent Texas population but did not confirm the protective effect. We further performed a mini meta-analysis for SNPs of TNFSF8 obtained from other four published lung cancer GWASs with 12  214 cases and 47  721 controls, and we found that only rs3181366 (r2=0.69 with the untyped rs2075533) was associated to lung cancer risk (P=0.008). Our findings suggest a possible role of novel TNFSF8 variants in susceptibility to lung cancer.

Duke Scholars

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

April 2011

Volume

32

Issue

4

Start / End Page

507 / 515

Location

England

Related Subject Headings

  • Texas
  • Risk
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Ki-1 Antigen
  • Humans
 

Citation

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Wei, S., Niu, J., Zhao, H., Liu, Z., Wang, L.-E., Han, Y., … Wei, Q. (2011). Association of a novel functional promoter variant (rs2075533 C>T) in the apoptosis gene TNFSF8 with risk of lung cancer--a finding from Texas lung cancer genome-wide association study. Carcinogenesis, 32(4), 507–515. https://doi.org/10.1093/carcin/bgr014
Wei, Sheng, Jiangong Niu, Hui Zhao, Zhensheng Liu, Li-E Wang, Younghun Han, Wei V. Chen, et al. “Association of a novel functional promoter variant (rs2075533 C>T) in the apoptosis gene TNFSF8 with risk of lung cancer--a finding from Texas lung cancer genome-wide association study.Carcinogenesis 32, no. 4 (April 2011): 507–15. https://doi.org/10.1093/carcin/bgr014.
Wei S, Niu J, Zhao H, Liu Z, Wang L-E, Han Y, Chen WV, Amos CI, Rafnar T, Sulem P, Stefansson K, Landi MT, Caporaso NE, Albanes D, Thun MJ, McKay JD, Brennan P, Wang Y, Houlston RS, Spitz MR, Wei Q. Association of a novel functional promoter variant (rs2075533 C>T) in the apoptosis gene TNFSF8 with risk of lung cancer--a finding from Texas lung cancer genome-wide association study. Carcinogenesis. 2011 Apr;32(4):507–515.
Journal cover image

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

April 2011

Volume

32

Issue

4

Start / End Page

507 / 515

Location

England

Related Subject Headings

  • Texas
  • Risk
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Ki-1 Antigen
  • Humans