Polymorphic loci of E2F2, CCND1 and CCND3 are associated with HER2 status of breast tumors.
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.
Justenhoven
Christina
C
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
Pierl
Christiane B
CB
Haas
Susanne
S
Fischer
Hans-Peter
HP
Hamann
Ute
U
Baisch
Christian
C
Harth
Volker
V
Spickenheuer
Anne
A
Rabstein
Sylvia
S
Vollmert
Caren
C
Illig
Thomas
T
Pesch
Beate
B
Brüning
Thomas
T
Dippon
Jürgen
J
Ko
Yon-Dschun
YD
Brauch
Hiltrud
H
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
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