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dc.contributor.authorLiu, H
dc.contributor.authorLiu, Z
dc.contributor.authorWang, Y
dc.contributor.authorStinchcombe, TE
dc.contributor.authorOwzar, K
dc.contributor.authorHan, Y
dc.contributor.authorHung, RJ
dc.contributor.authorBrhane, Y
dc.contributor.authorMcLaughlin, J
dc.contributor.authorBrennan, P
dc.contributor.authorBickeböller, H
dc.contributor.authorRosenberger, A
dc.contributor.authorHoulston, RS
dc.contributor.authorCaporaso, N
dc.contributor.authorLandi, MT
dc.contributor.authorBrüske, I
dc.contributor.authorRisch, A
dc.contributor.authorWu, X
dc.contributor.authorYe, Y
dc.contributor.authorChristiani, DC
dc.contributor.authorAmos, CI
dc.contributor.authorWei, Q
dc.contributor.authorTransdisciplinary Research in Cancer of the Lung (TRICL) Research Team
dc.date.accessioned2017-04-13T09:59:17Z
dc.date.issued2017-05
dc.identifier.citationCarcinogenesis, 2017, 38 (5), pp. 541 - 551
dc.identifier.issn0143-3334
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/596
dc.identifier.eissn1460-2180
dc.identifier.doi10.1093/carcin/bgx033
dc.description.abstractCullin-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.
dc.formatPrint
dc.format.extent541 - 551
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectTransdisciplinary Research in Cancer of the Lung (TRICL) Research Team
dc.subjectHumans
dc.subjectLung Neoplasms
dc.subjectGenetic Predisposition to Disease
dc.subjectCarrier Proteins
dc.subjectOdds Ratio
dc.subjectRisk
dc.subjectRisk Factors
dc.subjectCase-Control Studies
dc.subjectGene Expression Profiling
dc.subjectComputational Biology
dc.subjectDNA Methylation
dc.subjectLinkage Disequilibrium
dc.subjectPolymorphism, Single Nucleotide
dc.subjectEuropean Continental Ancestry Group
dc.subjectGenetic Variation
dc.subjectGenome-Wide Association Study
dc.subjectGenetic Association Studies
dc.titleFunctional variants in DCAF4 associated with lung cancer risk in European populations.
dc.typeJournal Article
dcterms.dateAccepted2017-03-24
rioxxterms.versionofrecord10.1093/carcin/bgx033
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCarcinogenesis
pubs.issue5
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.publication-statusPublished
pubs.volume38
pubs.embargo.termsNot known
icr.researchteamCancer Genomicsen_US
dc.contributor.icrauthorHoulston, Richarden


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