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白细胞介素-6基因启动子的分子筛查及-174G/C多态性对乳腺癌的影响

Molecular screening of interleukin-6 gene promoter and influence of -174G/C polymorphism on breast cancer.

作者信息

Chérel Michel, Campion Loïc, Bézieau Stéphane, Campone Mario, Charrier Josiane, Gaschet Joëlle, Ricolleau Gabriel, Gouraud Wilfried, Charbonnel Catherine, Jézéquel Pascal

机构信息

Département de Recherche en Cancérologie, Université de Nantes, INSERM U892, 9 quai Moncousu, 44035 Nantes Cedex, France.

出版信息

Cytokine. 2009 Sep;47(3):214-23. doi: 10.1016/j.cyto.2009.06.011. Epub 2009 Jul 28.

DOI:10.1016/j.cyto.2009.06.011
PMID:19640729
Abstract

Interleukin-6 (IL-6) is a cytokine involved in different physiologic and pathophysiologic processes including carcinogenesis. In 2003, a single nucleotide polymorphism (-174G/C) of the IL-6 gene promoter has been linked to breast cancer prognosis in node-positive (N+) breast cancer patients. Since, different studies have led to conflicting conclusions about its role as a prognostic and/or diagnostic marker. The primary aim of our study was to investigate the link between -174G/C polymorphism and breast cancer risk on the one hand, and -174G/C polymorphism and prognosis in different groups of patients: sporadic N+breast cancers (n=138), sporadic N- breast cancers (n=95) and familial breast cancer (n=60) on the other hand. The variables of interest were disease-free survival and overall survival. The secondary aim of the study was to screen IL-6 gene promoter using direct sequencing to identify new polymorphisms in our French Caucasian breast cancer population. No association or trend of association between -174G/C polymorphism of IL-6 gene promoter gene and breast cancer diagnosis or prognosis was shown, even in meta-analyses. Furthermore, we have identified four novel polymorphic sites in the IL-6 gene promoter region: -764G-->A, -757C-->T, -233T-->A, 15C-->A.

摘要

白细胞介素-6(IL-6)是一种参与包括致癌作用在内的不同生理和病理生理过程的细胞因子。2003年,IL-6基因启动子的单核苷酸多态性(-174G/C)已被证明与淋巴结阳性(N+)乳腺癌患者的乳腺癌预后相关。此后,不同的研究对于其作为预后和/或诊断标志物的作用得出了相互矛盾的结论。我们研究的主要目的一方面是调查-174G/C多态性与乳腺癌风险之间的联系,另一方面是调查-174G/C多态性与不同患者组的预后之间的联系:散发性N+乳腺癌(n = 138)、散发性N-乳腺癌(n = 95)和家族性乳腺癌(n = 60)。感兴趣的变量是无病生存期和总生存期。该研究的次要目的是通过直接测序筛选IL-6基因启动子,以在我们的法国白种人乳腺癌人群中鉴定新的多态性。即使在荟萃分析中,也未显示IL-6基因启动子基因的-174G/C多态性与乳腺癌诊断或预后之间存在关联或关联趋势。此外,我们在IL-6基因启动子区域鉴定了四个新的多态性位点:-764G→A、-757C→T、-233T→A、15C→A。

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