RGD Reference Report - Transcription deregulation at the 15q25 locus in association with lung adenocarcinoma risk. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Transcription deregulation at the 15q25 locus in association with lung adenocarcinoma risk.

Authors: Falvella, Felicia S  Galvan, Antonella  Frullanti, Elisa  Spinola, Monica  Calabrò, Elisa  Carbone, Antonino  Incarbone, Matteo  Santambrogio, Luigi  Pastorino, Ugo  Dragani, Tommaso A 
Citation: Falvella FS, etal., Clin Cancer Res. 2009 Mar 1;15(5):1837-42. doi: 10.1158/1078-0432.CCR-08-2107. Epub 2009 Feb 17.
RGD ID: 150524354
Pubmed: PMID:19223495   (View Abstract at PubMed)
DOI: DOI:10.1158/1078-0432.CCR-08-2107   (Journal Full-text)


PURPOSE: We characterized the candidacy of the six candidate genes mapping in the chromosome 15q25 locus, which was previously reported as associated with lung cancer risk, and confirmed the locus association with lung cancer risk in an Italian population of lung adenocarcinoma patients and controls.
EXPERIMENTAL DESIGN: We did a quantitative analysis of mRNA levels of IREB2 (iron-responsive element-binding protein 2), LOC123688, PMSA4 [proteasome (prosome, macropain) subunit alpha type 4], CHRNB4 (cholinergic receptor nicotinic beta 4), CHRNA3 (cholinergic receptor nicotinic alpha 3), and CHRNA5 (cholinergic receptor nicotinic alpha 5) genes in paired normal lung and lung adenocarcinoma tissue, and an immunohistochemical localization of CHRNA3- and CHRNA5-encoded proteins. We also examined the association of CHRNA5 D398N polymorphism with lung cancer risk and with CHRNA5 mRNA levels in the normal lung.
RESULTS: Expression analysis of the six candidate genes mapping in the lung cancer risk-associated chromosome 15q25 locus revealed a 30-fold up-regulation of the gene encoding the CHRNA5 subunit and a 2-fold down-regulation of the CHRNA3 subunit in lung adenocarcinoma as compared with the normal lung. The expression of the four other candidate genes resulted either unchanged or absent. The carrier status of the 398N allele at the D398N polymorphism of the CHRNA5 gene was associated with lung adenocarcinoma risk (odds ratio, 1.5; 95% confidence interval, 1.2-2.0) in a population-based series of lung adenocarcinoma patients (n=467) and healthy controls (n=739). Analysis of a family-based series of nonsmoker lung cancer cases (n=80) and healthy sib controls (n=80) indicated a similar trend. In addition, the same D398N variation correlated with CHRNA5 mRNA levels in normal lung of adenocarcinoma patients.
CONCLUSIONS: Our results point to the candidacy of the CHRNA5 gene for the 15q25 locus.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung adenocarcinoma  IEP 150524354mRNA and protein:decreased expression:lungRGD 
lung adenocarcinoma  IAGP 150524354DNA:SNP:cds: p.D398N (rs1696996)(human)RGD 
lung adenocarcinoma  ISOCHRNA3 (Homo sapiens)150524354; 150524354mRNA and protein:decreased expression:lungRGD 
lung adenocarcinoma  ISOCHRNA5 (Homo sapiens)150524354; 150524354DNA:SNP:cds: p.D398N (rs1696996)(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Chrna3  (cholinergic receptor nicotinic alpha 3 subunit)
Chrna5  (cholinergic receptor nicotinic alpha 5 subunit)

Genes (Mus musculus)
Chrna3  (cholinergic receptor, nicotinic, alpha polypeptide 3)
Chrna5  (cholinergic receptor, nicotinic, alpha polypeptide 5)

Genes (Homo sapiens)
CHRNA3  (cholinergic receptor nicotinic alpha 3 subunit)
CHRNA5  (cholinergic receptor nicotinic alpha 5 subunit)


Additional Information