| 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. | |
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MedLine Citation:
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PMID: 21292647 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sheng Wei; Jiangong Niu; Hui Zhao; Zhensheng Liu; Li-E Wang; Younghun Han; Wei V Chen; Christopher I Amos; Thorunn Rafnar; Patrick Sulem; Kari Stefansson; Maria T Landi; Neil E Caporaso; Demetrius Albanes; Michael J Thun; James D McKay; Paul Brennan; Yufei Wang; Richard S Houlston; Margaret R Spitz; Qingyi Wei |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-02-02 |
Journal Detail:
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Title: Carcinogenesis Volume: 32 ISSN: 1460-2180 ISO Abbreviation: Carcinogenesis Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-31 Completed Date: 2011-06-09 Revised Date: 2012-10-09 |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
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Languages: eng Pagination: 507-15 Citation Subset: IM |
Affiliation:
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Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Antigens, CD30 / physiology Apoptosis CD30 Ligand / genetics* Cell Line, Tumor Female Genome-Wide Association Study* Humans Lung Neoplasms / etiology, genetics* Male Middle Aged Polymorphism, Single Nucleotide* Promoter Regions, Genetic* Risk Texas |
| Grant Support | |
ID/Acronym/Agency:
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P30 CA016672/CA/NCI NIH HHS; R01 CA121197/CA/NCI NIH HHS; R01 CA133996/CA/NCI NIH HHS; R01CA055769/CA/NCI NIH HHS; R01CA121197/CA/NCI NIH HHS; R01CA127219/CA/NCI NIH HHS; R01CA131274/CA/NCI NIH HHS; R01ES011740/ES/NIEHS NIH HHS; U19 CA148127/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD30; 0/CD30 Ligand; 0/TNFSF8 protein, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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