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

<p>Abstract</p> <p>Background</p> <p>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 Endost...

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Main Authors: Cox Angela, Globe Jenny, Cross Simon S, Balasubramanian Sabapathy P, Brown Nicola J, Reed Malcolm W
Format: Article
Language:English
Published: BMC 2007-06-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/7/107
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author Cox Angela
Globe Jenny
Cross Simon S
Balasubramanian Sabapathy P
Brown Nicola J
Reed Malcolm W
author_facet Cox Angela
Globe Jenny
Cross Simon S
Balasubramanian Sabapathy P
Brown Nicola J
Reed Malcolm W
author_sort Cox Angela
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>
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spelling doaj.art-d2d71bc195de4da0a69cb5cd5b2e3c112022-12-22T03:20:33ZengBMCBMC Cancer1471-24072007-06-017110710.1186/1471-2407-7-107Endostatin gene variation and protein levels in breast cancer susceptibility and severityCox AngelaGlobe JennyCross Simon SBalasubramanian Sabapathy PBrown Nicola JReed Malcolm W<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>http://www.biomedcentral.com/1471-2407/7/107
spellingShingle Cox Angela
Globe Jenny
Cross Simon S
Balasubramanian Sabapathy P
Brown Nicola J
Reed Malcolm W
Endostatin gene variation and protein levels in breast cancer susceptibility and severity
BMC Cancer
title Endostatin gene variation and protein levels in breast cancer susceptibility and severity
title_full Endostatin gene variation and protein levels in breast cancer susceptibility and severity
title_fullStr Endostatin gene variation and protein levels in breast cancer susceptibility and severity
title_full_unstemmed Endostatin gene variation and protein levels in breast cancer susceptibility and severity
title_short Endostatin gene variation and protein levels in breast cancer susceptibility and severity
title_sort endostatin gene variation and protein levels in breast cancer susceptibility and severity
url http://www.biomedcentral.com/1471-2407/7/107
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AT balasubramaniansabapathyp endostatingenevariationandproteinlevelsinbreastcancersusceptibilityandseverity
AT brownnicolaj endostatingenevariationandproteinlevelsinbreastcancersusceptibilityandseverity
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