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Polymorphic loci of E2F2, CCND1 and CCND3 are associated with HER2 status of breast tumors
Author(s) -
Justenhoven Christina,
Pierl Christiane B.,
Haas Susanne,
Fischer HansPeter,
Hamann Ute,
Baisch Christian,
Harth Volker,
Spickenheuer Anne,
Rabstein Sylvia,
Vollmert Caren,
Illig Thomas,
Pesch Beate,
Brüning Thomas,
Dippon Jürgen,
Ko YonDschun,
Brauch Hiltrud
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24198
Subject(s) - breast cancer , genotype , oncology , cyclin d1 , medicine , cancer research , biology , cancer , gene , cell cycle , genetics
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. © 2008 Wiley‐Liss, Inc.