Polymorphisms of survivin promoter are associated with risk of esophageal squamous cell carcinoma
Polymorphisms of survivin promoter are associated with risk of esophageal squamous cell carcinoma
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生存素启动子多态性与食管鳞状细胞癌的风险相关
DOI：
10.1007/s00432-009-0575-7
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发表时间：
2009-10-01
影响因子：
3.6
通讯作者：
Bai, Yun
中科院分区：
文献类型：
--
作者：
Yang, Xiaoya;Xiong, Gang;Bai, Yun
目的：survivin在正常成人组织中是检测不到的，但在各种癌症中被证明是过表达的，并被认为是恶性肿瘤的标志。增加survivin表达的多态性是食管癌发生的潜在危险因素。本研究的目的是对食管鳞状细胞癌患者和对照组的survivin启动子多态性进行基因分型，即- 31G/C、- 241T/C、- 625G/C和- 644T/C，并确定个体遗传变异与食管鳞状细胞癌（ESCC）易感性之间的可能关联。方法采用半定量RT-PCR法检测survivin在肿瘤组织中的表达。共有221名中国ESCC患者和268名无癌对照进行了survivin启动子的四种多态性评估。采用PCR-RFLP技术（−31G/C,−241T/C）或引物限制性内切分析- pcr法（−644T/C,−625G/C）鉴定多态性。结果与- 625GG基因型相比，- 625CC基因型与ESCC风险显著升高相关（OR = 2.404, 95% CI = 1.342 ~ 4.307）。此外，在不同−625G/C变异亚组之间，食管鳞状细胞癌组织中survivin的表达也存在显著差异。当我们检测survivin启动子多态性的综合效应时，−644T/C-−625G/C-−31G/C构建的单倍型显示出与ESCC的显著相关性（globalP= 0.0034）。−644T-−625C-−31C是ESCC的危险单倍型（P<0.001），−644T-−625G-−31C是ESCC的保护性单倍型（P= 0.004）。结论survivin启动子多态性−625G/C可能通过影响survivin的表达影响中国人群ESCC易感性。
PurposeSurvivin is undetectable in normal adult tissues, but has been shown to be overexpressed in various cancers and has been regarded as a marker of malignancy. Polymorphisms which increase the expression of survivin are potential risk factors for esophageal carcinogenesis. The aim of this study is to genotype the survivin promoter polymorphisms namely −31G/C, −241T/C, −625G/C, and −644T/C in esophageal squamous cell cancer patients and controls and to identify a possible association between individual genetic variation and susceptibility to esophageal squamous cell carcinoma (ESCC).MethodsThe expression of survivin in cancer tissues was detected by semiquantitative RT-PCR. A total of 221 Chinese ESCC patients and 268 cancer-free controls were evaluated for the four polymorphisms in survivin promoter. Polymorphisms were identified using the PCR–RFLP technique (−31G/C, −241T/C) or primer-introduced restriction analysis-PCR assay (−644T/C, −625G/C).ResultsCompared with the −625GG genotype, the −625CC genotype was associated with significant elevated risk of ESCC (OR = 2.404, 95% CI = 1.342–4.307). Furthermore, significant difference in survivin expression in esophageal squamous cell cancer tissues was found between subgroups with different −625G/C variants. When we examined the combined effect of the survivin promoter polymorphisms, the haplotypes constructed of −644T/C-−625G/C-−31G/C revealed significant associations with ESCC (globalP= 0.0034). −644T-−625C-−31C was a risk haplotype for ESCC (P<0.001) and −644T-−625G-−31C was a protective haplotype (P= 0.004).ConclusionsOur finding suggested that survivin promoter polymorphisms −625G/C might influence the susceptibility to ESCC in the Chinese population, maybe by influencing survivin expression.