title: Polymorphic loci of E2F2, CCND1 and CCND3 are associated with HER2 status of breast tumors.
abstract: Overexpression of the human epidermal growth factor receptor 2 (HER2) in breast tumors is associated with bad prognosis. Therefore, it is highly relevant to further improve understanding of the regulatory mechanisms of HER2 expression. In addition to gene amplification, transcriptional regulation plays a crucial role in HER2 overexpression. In this study, we analyzed 3 polymorphisms E2F2_-5368_A>G, CCND1_870_A>G and CCND3_-677_C>T located in genes involved in cell cycle regulation in the GENICA population-based and age-matched breast cancer case-control study from Germany. We genotyped 1,021 cases and 1,015 controls by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Statistical analyses were performed by conditional logistic regression. We observed no differences in genotype frequencies between breast cancer cases and controls. Subgroup analysis showed associations between carriers of the E2F2_-5368_G allele (OR: 0.60, 95% CI: 0.42-0.85), carriers of the CCND1_870_G allele (OR: 0.66, 95% CI: 0.45-0.96) and carriers of the CCND3_-677_T allele (OR: 1.72, 95% CI: 1.20-2.49) and HER2 expression in breast tumors. This finding points to an association of an increased expression of these cell cycle regulators with lower expression of HER2. An explanation for this observation might be that low expression of E2F2, CCND1 and CCND3 decrease levels of factors down-regulating HER2. We conclude that the analyzed polymorphisms located in E2F2, CCND1 and CCND3 are potential markers for HER2 status of breast tumors.
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Justenhoven
authors.forename: Christiane B
authors.initials: CB
authors.lastname: Pierl
authors.forename: Susanne
authors.initials: S
authors.lastname: Haas
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Fischer
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
authors.forename: Christian
authors.initials: C
authors.lastname: Baisch
authors.forename: Volker
authors.initials: V
authors.lastname: Harth
authors.forename: Anne
authors.initials: A
authors.lastname: Spickenheuer
authors.forename: Sylvia
authors.initials: S
authors.lastname: Rabstein
authors.forename: Caren
authors.initials: C
authors.lastname: Vollmert
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Beate
authors.initials: B
authors.lastname: Pesch
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.forename: Jürgen
authors.initials: J
authors.lastname: Dippon
authors.forename: Yon-Dschun
authors.initials: YD
authors.lastname: Ko
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Brauch
mesh_terms: D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D056743:Cyclin D3; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D050703:E2F2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D005858:Germany; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019938:Cyclin D1; D056743:Cyclin D3; D016213:Cyclins; D050703:E2F2 Transcription Factor; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; C530104:CCND1 protein, human; C534696:CCND3 protein, human; C493761:E2F2 protein, human; C508053:ERBB2 protein, human