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表皮生长因子启动子单核苷酸多态性、血浆表皮生长因子水平与中国女性患乳腺癌风险

EGF promoter SNPs, plasma EGF levels and risk of breast cancer in Chinese women.

作者信息

Wang Yan, Tian Tian, Hu Zhibin, Tang Jinhai, Wang Shui, Wang Xuechen, Qin Jianwei, Huo Xiang, Gao Jun, Ke Qiao, Jin Guangfu, Ma Hongxia, Wang Xinru, Shen Hongbing

机构信息

Laboratory of Reproductive Medicine, Cancer Research Center of Nanjing Medical University, Nanjing, China.

出版信息

Breast Cancer Res Treat. 2008 Sep;111(2):321-7. doi: 10.1007/s10549-007-9784-4. Epub 2007 Oct 17.

Abstract

Epidermal growth factor (EGF), a potent mitogenic peptide, plays an important role in the development of cancers, including breast cancer. Previous studies showed that plasma EGF levels may influence the risk of cancer. In the current study, we hypothesized that genetic variants in the promoter region of EGF may influence plasma EGF levels and therefore are associated with breast cancer susceptibility. We genotyped three EGF polymorphisms (G61A, G-1380A, and A-1744G) in the promoter region by PCR-RFLP and measured plasma EGF levels using an enzyme immunoassay in a case-control study of Chinese women. We found that the mean plasma EGF levels in breast cancer patients (249.06 +/- 197.54 pg/ml) were significantly lower than those in controls (982.41 +/- 375.57 pg/ml, P < 0.001). There was a significant difference of plasma EGF levels among different genotypes carriers of the G-1380A locus in 654 controls (P = 0.007). After adjustment for age, body mass index, family history of cancer, age at menarche, and menopause status, EGF-1380AA carriers had significantly higher plasma EGF levels than -1380GG carriers did (P = 0.003). However, we did not find any significant associations between the three EGF polymorphisms (G61A, G-1380A, and A-1744G) and the risk of breast cancer. These findings indicated that plasma EGF levels served as a protective marker against breast cancer in our study and EGF G-1380A variant might be a modifier on it. Further studies are warranted to verify these findings.

摘要

表皮生长因子(EGF)是一种强效促有丝分裂肽,在包括乳腺癌在内的癌症发展过程中发挥着重要作用。先前的研究表明,血浆EGF水平可能会影响患癌风险。在本研究中,我们假设EGF启动子区域的基因变异可能会影响血浆EGF水平,因此与乳腺癌易感性相关。在一项针对中国女性的病例对照研究中,我们通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对启动子区域的三种EGF多态性(G61A、G-1380A和A-1744G)进行了基因分型,并使用酶免疫测定法测量了血浆EGF水平。我们发现,乳腺癌患者的血浆EGF平均水平(249.06±197.54 pg/ml)显著低于对照组(982.41±375.57 pg/ml,P<0.001)。在654名对照组中,G-1380A位点不同基因型携带者的血浆EGF水平存在显著差异(P=0.007)。在调整年龄、体重指数、癌症家族史、初潮年龄和绝经状态后,EGF-1380AA基因型携带者的血浆EGF水平显著高于-1380GG基因型携带者(P=0.003)。然而,我们未发现三种EGF多态性(G61A、G-1380A和A-1744G)与乳腺癌风险之间存在任何显著关联。这些发现表明,在我们的研究中,血浆EGF水平是乳腺癌的一个保护性标志物,而EGF G-1380A变异可能是其一个修饰因素。需要进一步研究来验证这些发现。

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