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Endostatin gene variation and protein levels in breast cancer susceptibility and severity

Balasubramanian, S., Cross, S., Globe, J., Cox, A., Brown, N. and Reed, M. (2007) Endostatin gene variation and protein levels in breast cancer susceptibility and severity. BMC Cancer, 7 (1). p. 107. ISSN 1471-2407

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Abstract

BACKGROUND:

Endostatin is a potent endogenous anti-angiogenic agent which inhibits tumour growth. A non-synonymous coding polymorphism in the Endostatin gene is thought to affect Endostatin activity. We aimed to determine the role of this Endostatin polymorphism in breast cancer pathogenesis and any influence on serum Endostatin levels in healthy volunteers. Endostatin protein expression on a breast cancer micro array was also studied to determine any relationship to genotype and to breast cancer prognosis.

METHODS:

The 4349G > A (coding non-synonymous) polymorphism in exon 42 of the Endostatin gene was genotyped in approximately 846 breast cancer cases and 707 appropriate controls. In a separate healthy cohort of 57 individuals, in addition to genotyping, serum Endostatin levels were measured using enzyme linked immunosorbant assay (ELISA). A semi-quantitative assessment of Endostatin protein expression on immunostained tissue micro arrays (TMA) constructed from breast cancer samples of patients with genotype data was performed.

RESULTS:

The rare allele (A) was significantly associated with invasive breast cancers compared to non-invasive tumours (p = 0.03), but there was no association with tumour grade, nodal status, vascular invasion or overall survival. There was no association with breast cancer susceptibility. Serum Endostatin levels and Endostatin protein expression on the tissue micro array were not associated with genotype.

CONCLUSION:

The Endostatin 4349A allele is associated with invasive breast cancer. The Endostatin 4349G > A polymorphism however does not appear to be associated with breast cancer susceptibility or severity in invasive disease. By studying circulating levels and tumour Endostatin protein expression, we have shown that any influence of this polymorphism is unlikely to be through an effect on the levels of protein produced.

Item Type: Article
Copyright, Publisher and Additional Information: © 2007 Balasubramanian et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology (Sheffield)
Depositing User: Sheffield Import
Date Deposited: 02 Oct 2009 13:10
Last Modified: 08 Oct 2009 09:19
Published Version: http://www.biomedcentral.com/1471-2407/7/107
Status: Published
Publisher: Biomed Central
Identification Number: 10.1186/1471-2407-7-107
URI: http://eprints.whiterose.ac.uk/id/eprint/9604

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