Balasubramanian Sabapathy P, Cross Simon S, Globe Jenny, Cox Angela, Brown Nicola J, Reed Malcolm W
Academic Surgical Oncology Unit, University of Sheffield, Sheffield, UK.
BMC Cancer. 2007 Jun 22;7:107. doi: 10.1186/1471-2407-7-107.
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.
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.
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.
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.
内皮抑素是一种有效的内源性抗血管生成剂，可抑制肿瘤生长。内皮抑素基因中的一个非同义编码多态性被认为会影响内皮抑素的活性。我们旨在确定这种内皮抑素多态性在乳腺癌发病机制中的作用，以及对健康志愿者血清内皮抑素水平的任何影响。还研究了乳腺癌微阵列上的内皮抑素蛋白表达，以确定其与基因型及乳腺癌预后的关系。
对约846例乳腺癌病例和707例合适对照进行内皮抑素基因第42外显子4349G>A（编码非同义）多态性基因分型。在一个由57名个体组成的独立健康队列中，除基因分型外，还使用酶联免疫吸附测定（ELISA）测量血清内皮抑素水平。对由有基因型数据的患者乳腺癌样本构建的免疫染色组织微阵列（TMA）上的内皮抑素蛋白表达进行半定量评估。
与非侵袭性肿瘤相比，罕见等位基因（A）与侵袭性乳腺癌显著相关（p = 0.03），但与肿瘤分级、淋巴结状态、血管侵犯或总生存期无关。与乳腺癌易感性无关。血清内皮抑素水平和组织微阵列上的内皮抑素蛋白表达与基因型无关。
内皮抑素4349A等位基因与侵袭性乳腺癌相关。然而，内皮抑素4349G>A多态性似乎与乳腺癌易感性或侵袭性疾病的严重程度无关。通过研究循环水平和肿瘤内皮抑素蛋白表达，我们发现这种多态性的任何影响不太可能是通过对产生的蛋白水平的影响。
