Association of transforming growth factor-β1 gene polymorphisms with genetic susceptibility to nasopharyngeal carcinoma

Association of transforming growth factor-β1 gene polymorphisms with genetic susceptibility to nasopharyngeal carcinoma
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DOI:
10.1016/j.cca.2007.02.008
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发表时间:
2007-05-01
影响因子:
5
通讯作者:
Zhang, Lin
Zhang, Lin
中科院分区:
医学3区
文献类型:
--
作者:
Wei, Ye-Sheng;Zhu, Yin-Hua;Zhang, Lin

文献摘要

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背景:鼻咽癌(NPC)是多因素影响的,遗传背景可能是一个关键的病因。转化生长因子-β1(TGF-β1)是一种多功能细胞因子,它在癌症发展的后期促进肿瘤生长和转移。 TGF-β1 基因 DNA 序列的变异可能导致 TGF-β1 产生和/或活性改变,因此这可以调节个体对 NPC 的易感性。为了检验这一假设,我们研究了中国人群中 TGF-β 1 多态性及其单倍型与 NPC 风险的关联。方法:我们分析了 108 名鼻咽癌患者和 120 名年龄和性别匹配的对照者中 108 名鼻咽癌患者和 120 名年龄和性别匹配对照者中 TGF-β 1 基因启动子外显子 1 的 2 个单核苷酸多态性 (SNP) - 509C/T 和 869T/C (Leu10Pro)。中国人群,采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)策略。结果:病例与对照间TGFβ1基因-509C/T和869T/C(Leu10Pro)多态性的基因型和等位基因分布存在显着差异。与非携带者相比,-509T 和 869C 等位基因携带者与鼻咽癌风险显着增加相关(分别为 OR=1.64、95% CI、1.13-2.39、P=0.009 和 OR=1.70、95% CI、1.17-2.46、P=0.006)。与基因分型分析的结果一致,与 - 509C/869T 单倍型相比, - 509T/869C 单倍型与 NPC 风险显着增加相关(OR 1.68;95% CI,1.14-2.48;P=0.009)。结论:TGF beta 1 - 509C/T 和869T/C多态性及其单倍型与鼻咽癌风险显着相关。我们的数据表明TGF-β 1 - 509C/T和869T/C多态性可以用作鼻咽癌的遗传易感性标记。 (c) 2007 Elsevier B.V. 保留所有权利。
Background: Nasopharyngeal cancer (NPC) is multifactorial, and the genetic background may be a crucial etiologic factor. Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine, it promotes tumor growth and metastasis in later stages of phase of cancer development. Variations in the DNA sequence in the TGF-beta 1 gene may lead to altered TGF beta 1 production and/or activity, and so this can modulate an individual's susceptibility to NPC. To test this hypothesis, we investigated the association of the TGF-beta 1 polymorphisms and their haplotypes with the risk of NPC in a Chinese population.Methods: We analyzed 2 single nucleotide polymorphisms (SNPs) of TGF beta 1 gene promoter - 509C/T and 869T/C (Leu10Pro) at exon one in 108 patients with NPC and 120 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy.Results: There were significant differences in the genotype and allele distribution of - 509C/T and 869T/C (Leu10Pro) polymorphisms of the TGF beta 1 gene among cases and controls. The - 509T and 869C alleles carriers were associated with a significantly increased risk of NPC as compared with the non-carriers (OR=1.64, 95% CI, 1.13-2.39, P=0.009 and OR=1.70, 95% CI, 1.17-2.46, P=0.006, respectively). Consistent with the results of the genotyping analyses, the - 509T/869C haplotype was associated with a significantly increased risk of NPC as compared with the - 509C/869T haplotype (OR 1.68; 95% CI, 1.14-2.48; P=0.009).Conclusion: TGF beta 1 - 509C/T and 869T/C polymorphisms, and their haplotypes are significantly associated with the risk of NPC. Our data suggests that TGF-beta 1 - 509C/T and 869T/C polymorphisms could be used as genetic susceptibility markers of the NPC. (c) 2007 Elsevier B.V. All rights reserved.