RGD Reference Report - Risk factors for breast cancer characterized by the estrogen receptor alpha A908G (K303R) mutation. - 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 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
Advanced Search (OLGA)

Risk factors for breast cancer characterized by the estrogen receptor alpha A908G (K303R) mutation.

Authors: Conway, K  Parrish, E  Edmiston, SN  Tolbert, D  Tse, CK  Moorman, P  Newman, B  Millikan, RC 
Citation: Conway K, etal., Breast Cancer Res. 2007;9(3):R36.
RGD ID: 8553052
Pubmed: PMID:17553133   (View Abstract at PubMed)
PMCID: PMC1929100   (View Article at PubMed Central)
DOI: DOI:10.1186/bcr1731   (Journal Full-text)

INTRODUCTION: Estrogen is important in the development of breast cancer, and its biological effects are mediated primarily through the two estrogen receptors alpha and beta. A point mutation in the estrogen receptor alpha gene, ESR1, referred to as A908G or K303R, was originally identified in breast hyperplasias and was reported to be hypersensitive to estrogen. We recently detected this mutation at a low frequency of 6% in invasive breast tumors of the Carolina Breast Cancer Study (CBCS). METHODS: In this report, we evaluated risk factors for invasive breast cancer classified according to the presence or absence of the ESR1 A908G mutation in the CBCS, a population-based case-control study of breast cancer among younger and older white and African-American women in North Carolina. Of the 653 breast tumors evaluated, 37 were ESR1 A908G mutation-positive and 616 were mutation-negative. RESULTS: ESR1 A908G mutation-positive breast cancer was significantly associated with a first-degree family history of breast cancer (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.15 to 6.28), whereas mutation-negative breast cancer was not. Comparison of the two case subgroups supported this finding (OR = 2.65, 95% CI = 1.15 to 6.09). There was also the suggestion that longer duration of oral contraceptive (OC) use (OR = 3.73, 95% CI = 1.16 to 12.03; Ptrend = 0.02 for use of more than 10 years) and recent use of OCs (OR = 3.63, 95% CI = 0.80 to 16.45; Ptrend = 0.10 for use within 10 years) were associated with ESR1 A908G mutation-positive breast cancer; however, ORs for comparison of the two case subgroups were not statistically significant. Hormone replacement therapy use was inversely correlated with mutation-negative breast cancer, but the effect on mutation-positive cancer was unclear due to the small number of postmenopausal cases whose tumors carried the mutation. Mutation-negative breast cancer was associated with several reproductive factors, including younger age at menarche (OR = 1.46, 95% CI = 1.09 to 1.94) and greater total estimated years of ovarian function (OR = 1.82, 95% CI = 1.21 to 2.74). CONCLUSION: These preliminary results suggest that OCs may interact with the ESR1 A908G mutant receptor to drive the development of some breast tumors.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ESR1Humanbreast cancer  IAGP DNA:SNP: :908A>G (p.K303R) (human)RGD 
Esr1Ratbreast cancer  ISOESR1 (Homo sapiens)DNA:SNP: :908A>G (p.K303R) (human)RGD 
Esr1Mousebreast cancer  ISOESR1 (Homo sapiens)DNA:SNP: :908A>G (p.K303R) (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Esr1  (estrogen receptor 1)

Genes (Mus musculus)
Esr1  (estrogen receptor 1 (alpha))

Genes (Homo sapiens)
ESR1  (estrogen receptor 1)


Additional Information