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环氧化酶-2 169C>G 和 8473T>C 基因多态性与乳腺癌中前列腺素 E2 水平的关系:一项病例对照研究。

Cyclooxygenase-2 169C>G and 8473T>C gene polymorphisms and prostaglandin E2 level in breast cancer: a case-control study.

机构信息

Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Egypt.

出版信息

Gene. 2013 Sep 25;527(2):601-5. doi: 10.1016/j.gene.2013.06.007. Epub 2013 Jun 18.

Abstract

AIMS

Cyclooxygenase 2 (COX-2) with the resulting prostaglandin E2 (PGE2) is linked to increased risk of human breast cancer (BC). The aim of this study was to determine COX-2 169C>G and 8473T>C gene polymorphisms and PGE2 level at various stages of BC clarifying the role of COX-2 gene polymorphism and PGE2 in relation to BC.

METHODS

The study population comprised 160 women at different stages of BC and 150 gender- and age-matched healthy control subjects. Plasma PGE2 was measured by ELISA, the COX-2 gene polymorphisms were determined using PCR-RFLP.

RESULTS

The variant alleles COX-2 169G and 8473C were significantly associated with BC susceptibility [OR=3.1, 95% CI (2.2-4.4), P<0.001 for 169C>G and OR=1.74, 95%CI (1.3-2.4), P=0.005 for 8473C]. However, both COX-2 gene polymorphisms were not associated with breast cancer stage. Plasma PGE2 levels were significantly increased in patients compared to the controls. In early and late stages of BC, there was a significant increase in the plasma PGE2 levels towards the presence of homozygous GG compared with homozygous CC (P<0.001) for 169 C>G, also towards the presence of CC than TT (P<0.001) for 8473T>C SNP.

CONCLUSION

The 169C>G and 8473T>C polymorphisms of the COX-2 gene were associated with the BC in Egyptian women. Furthermore, individuals with COX-2 169GG and 8473CC genotypes showed significant increase in plasma PGE2 levels. PGE2 levels may serve as a predictor of poor prognosis in patients with BC.

摘要

目的

环氧化酶 2(COX-2)及其产生的前列腺素 E2(PGE2)与人类乳腺癌(BC)的风险增加有关。本研究旨在确定 COX-2 169C>G 和 8473T>C 基因多态性以及 BC 不同阶段的 PGE2 水平,阐明 COX-2 基因多态性和 PGE2 与 BC 的关系。

方法

研究人群包括 160 名处于不同 BC 阶段的女性和 150 名性别和年龄匹配的健康对照者。通过 ELISA 测量血浆 PGE2,通过 PCR-RFLP 确定 COX-2 基因多态性。

结果

COX-2 169G 和 8473C 变异等位基因与 BC 易感性显著相关[比值比(OR)=3.1,95%置信区间(CI)(2.2-4.4),P<0.001 对于 169C>G 和 OR=1.74,95%CI(1.3-2.4),P=0.005 对于 8473C]。然而,这两种 COX-2 基因多态性与乳腺癌分期均无相关性。与对照组相比,患者的血浆 PGE2 水平显着升高。在 BC 的早期和晚期,与 169C>G 中的纯合 GG 相比,杂合 GG 中血浆 PGE2 水平显着升高(P<0.001),与 8473T>C SNP 中的 CC 相比,TT 中血浆 PGE2 水平显着升高(P<0.001)。

结论

COX-2 基因的 169C>G 和 8473T>C 多态性与埃及女性的 BC 相关。此外,COX-2 169GG 和 8473CC 基因型个体的血浆 PGE2 水平显着升高。PGE2 水平可能作为 BC 患者预后不良的预测指标。

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