Roles of functional NFKB1 and β-TrCP insertion/deletion polymorphisms in mRNA expression and epithelial ovarian cancer susceptibility
Roles of functional NFKB1 and β-TrCP insertion/deletion polymorphisms in mRNA expression and epithelial ovarian cancer susceptibility
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DOI：
10.4238/2013.march.11.6
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发表时间：
2013-01-01
影响因子：
0.4
通讯作者：
Tang, H.
中科院分区：
文献类型：
--
作者：
Huo, Z. H.;Zhong, H. J.;Tang, H.
上皮性卵巢癌（EOC）是所有妇科癌症中死亡的主要原因。核因子 kappa B (NF-kappa B) 参与癌发生和 EOC 的发展。含有 β-转导蛋白重复序列的蛋白 (β-TrCP) 是 NF-κ B 信号通路的正调节因子。最近的研究表明，NFKB1基因启动子区的-94 ins/del ATTG多态性和β-TrCP基因3'-非翻译区的9N ins/del多态性与多种癌症的易感性增加有关。我们检查了这两种多态性和 EOC 之间的潜在关联。使用 MassARRAY 系统确定了 187 名 EOC 患者和 221 名健康对照受试者的基因型。我们发现 -94 ins/del ATTG 基因型分布与 EOC 之间存在显着关联。与健康对照相比，EOC 患者中 -94 del ATTG 等位基因的频率显着降低。癌组织中NF-κB mRNA水平与-94 ins/del ATTG基因型显着相关。与 ATTG1/ATTG1 表型相比，ATTG2（插入）/ATTG2 纯合子和 ATTG1（缺失）/ATTG2 杂合子中 NF-kappa B mRNA 水平分别高出 2.089 倍和 1.257 倍。然而，我们没有发现中国人群中 β-TrCP 基因的 9N ins/del 多态性与 EOC 之间存在关联的证据。基于这些结果，我们认为 NF-kappa B -94 ins/del ATTG 多态性是 EOC 易感性的危险因素。
Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological cancers. Nuclear factor-kappa B (NF-kappa B) is involved in carcinogenesis and in the development of EOC. The beta-transducin repeat-containing protein (beta-TrCP) is a positive regulator of the NF-kappa B signaling pathway. Recent studies have indicated that the -94 ins/del ATTG polymorphism in the promoter region of the NFKB1 gene, and the 9N ins/del polymorphism in the 3'-untranslated region of the beta-TrCP gene are associated with increased susceptibility to a variety of cancers. We examined a potential association between these two polymorphisms and EOC. Genotypes were determined for 187 patients with EOC and 221 healthy control subjects, using the MassARRAY system. We found a significant association between the -94 ins/del ATTG genotype distribution and EOC. The frequency of the -94 del ATTG allele was significantly lower in EOC patients compared to healthy controls. The NF-kappa B mRNA level in cancer tissue was significantly correlated with -94 ins/del ATTG genotypes. Compared to the ATTG1/ATTG1 phenotype, the NF-kappa B mRNA level was 2.089 and 1.257 times higher in the ATTG2 (insertion)/ATTG2 homozygote and the ATTG1 (deletion)/ATTG2 heterozygote, respectively. However, we found no evidence of association between the 9N ins/del polymorphism of the beta-TrCP gene and EOC in this Chinese population. Based on these results, we suggest that the NF-kappa B -94 ins/del ATTG polymorphism is a risk factor for EOC susceptibility.