PubMed:16822847 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/16822847","sourcedb":"PubMed","sourceid":"16822847","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/16822847","text":"FGFR4 Arg388 allele is associated with resistance to adjuvant therapy in primary breast cancer.\nPURPOSE: A recent study presented first evidence that a single nucleotide polymorphism (SNP) at codon 388 of fibroblast growth factor receptor 4 (FGFR4) gene, causing a transmembrane domain missense mutation (Gly388Arg), is associated with disease outcome in node-positive breast cancer. This article addresses the clinical relevance of this SNP, FGFR4 genotype, phenotype, and HER2 regarding patient outcome and influence of adjuvant systemic therapy in a substantial primary breast cancer collective (n = 372; median follow-up, 94.5 months).\nMETHODS: Polymerase chain reaction restriction fragment length polymorphism analysis of germ-line polymorphism was performed in uninvolved lymph nodes; FGFR4 and HER2 expression were assessed immunohistochemically in tissue microarrays.\nRESULTS: In 51% of patients, homo- or heterozygous Arg388 allele was present. No correlation existed between FGFR4 genotype and expression or HER2 status. In node-negative patients, FGFR4 genotype was not correlated with disease outcome. In node-positive patients, however, FGFR4 Arg388 was significantly associated with poor disease-free survival (DFS; P = .02) and overall survival (OS; P = .04). Notably, this association seems to be attributable to relatively poor therapy response in Arg388 carriers, reflected in their significantly shorter DFS (P = .02) and OS (P = .045) among patients receiving adjuvant systemic therapy. It is also seen as a significant interaction term in a multivariate proportional hazards model with Arg388 carriers having only about half as much benefit from adjuvant systemic therapy as wild-type carriers.\nCONCLUSION: According to this study, FGFR4 Arg388 genotype is a marker for breast cancer progression in patients with adjuvant systemic therapy, particularly chemotherapy, and thus may indicate therapy resistance.","tracks":[{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":1754,"end":1759},"obj":"gene:2264"},{"id":"T1","span":{"begin":1792,"end":1805},"obj":"disease:C0006142"},{"id":"T2","span":{"begin":1754,"end":1759},"obj":"gene:2264"},{"id":"T3","span":{"begin":1792,"end":1805},"obj":"disease:C0678222"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"}]},{"project":"DisGeNET5_variant_disease","denotations":[{"id":"16822847-1#200#209#geners351855","span":{"begin":305,"end":314},"obj":"geners351855"},{"id":"16822847-1#264#277#diseaseC0006142","span":{"begin":369,"end":382},"obj":"diseaseC0006142"},{"id":"16822847-1#264#277#diseaseC0678222","span":{"begin":369,"end":382},"obj":"diseaseC0678222"}],"relations":[{"id":"200#209#geners351855264#277#diseaseC0006142","pred":"associated_with","subj":"16822847-1#200#209#geners351855","obj":"16822847-1#264#277#diseaseC0006142"},{"id":"200#209#geners351855264#277#diseaseC0678222","pred":"associated_with","subj":"16822847-1#200#209#geners351855","obj":"16822847-1#264#277#diseaseC0678222"}],"attributes":[{"subj":"16822847-1#200#209#geners351855","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"16822847-1#264#277#diseaseC0006142","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"16822847-1#264#277#diseaseC0678222","pred":"source","obj":"DisGeNET5_variant_disease"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"16822847-0#0#5#gene2264","span":{"begin":792,"end":797},"obj":"gene2264"},{"id":"16822847-0#81#94#diseaseC0006142","span":{"begin":1637,"end":1805},"obj":"diseaseC0006142"},{"id":"16822847-0#81#94#diseaseC0678222","span":{"begin":1637,"end":1805},"obj":"diseaseC0678222"},{"id":"16822847-2#90#94#gene2064","span":{"begin":474,"end":478},"obj":"gene2064"},{"id":"16822847-2#189#202#diseaseC0006142","span":{"begin":573,"end":586},"obj":"diseaseC0006142"},{"id":"16822847-2#189#202#diseaseC0678222","span":{"begin":573,"end":586},"obj":"diseaseC0678222"}],"relations":[{"id":"0#5#gene226481#94#diseaseC0006142","pred":"associated_with","subj":"16822847-0#0#5#gene2264","obj":"16822847-0#81#94#diseaseC0006142"},{"id":"0#5#gene226481#94#diseaseC0678222","pred":"associated_with","subj":"16822847-0#0#5#gene2264","obj":"16822847-0#81#94#diseaseC0678222"},{"id":"90#94#gene2064189#202#diseaseC0006142","pred":"associated_with","subj":"16822847-2#90#94#gene2064","obj":"16822847-2#189#202#diseaseC0006142"},{"id":"90#94#gene2064189#202#diseaseC0678222","pred":"associated_with","subj":"16822847-2#90#94#gene2064","obj":"16822847-2#189#202#diseaseC0678222"}],"attributes":[{"subj":"16822847-0#0#5#gene2264","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"16822847-0#81#94#diseaseC0006142","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"16822847-0#81#94#diseaseC0678222","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"16822847-2#90#94#gene2064","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"16822847-2#189#202#diseaseC0006142","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"16822847-2#189#202#diseaseC0678222","pred":"source","obj":"DisGeNET5_gene_disease"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET","color":"#93ecae","default":true},{"id":"DisGeNET5_variant_disease","color":"#ec9493"},{"id":"DisGeNET5_gene_disease","color":"#93acec"}]}]}}