Polymorphic loci of E2F2, CCND1 and CCND3 are associated with HER2 status of breast tumors

Scientific Paper

Expression Proteomics, Clinical Proteomics

10.1002/ijc.24198

MALDI-TOF

2009

autoflex

Christina Justenhoven1, Christiane B. Pierl2, Susanne Haas3, Hans-Peter Fischer3, Ute Hamann4, Christian Baisch5, Volker Harth5, Anne Spickenheuer5, Sylvia Rabstein5, Caren Vollmert6, Thomas Illig6, Beate Pesch7, Thomas Br€uning7, J€urgen Dippon8, Yon-Dschun Ko5 and Hiltrud Brauch1*

Int. J. Cancer: 124, 2077–2081 (2009)

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.

link to article

Related Products

Download