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HSP70-同源基因变异与前列腺癌风险的关联。

Association of HSP70-hom genetic variant with prostate cancer risk.

作者信息

Sfar Sana, Saad Hamadi, Mosbah Faouzi, Chouchane Lotfi

机构信息

Department of Molecular Immuno-Oncology, Faculty of Medicine, Monastir, Tunisia.

出版信息

Mol Biol Rep. 2008 Sep;35(3):459-64. doi: 10.1007/s11033-007-9107-1. Epub 2007 Jun 20.

Abstract

Because of the importance of androgens to prostate cancer (PCa) development, several candidate genes along androgen pathway have been under intensive study. Given the role of the molecular chaperone HSP70 in the regulation of the androgen receptor (AR) transactivation function, we first chose to explore the association between the HSP70-hom functional genetic variant (+2437 T > C) and prostate cancer risk by genotyping DNA samples from 101 unselected PCa patients and 105 healthy men. There was a trend towards lower frequency of TC and CC genotypes among patients when compared with healthy controls, however the difference did not reach the statistical significance (TC genotype: OR = 0.53, P = 0.05; CC genotype: OR = 0.42, P = 0.16). Moreover, individuals carrying at least one C allele have a statistically significant lower susceptibility for PCa (OR = 0.51 (0.26-0.97); P = 0.02). Since some factors may influence tumor progression rather than initiation, we also examined the relationship between the HSP70-hom polymorphism and the clinical characteristics of the malignancy at the time of diagnosis. The stratified analysis of the genotypes with the clinical stage and tumor grade showed that there was no significant difference in the risk estimates according to prognostic indicators of PCa disease in our population study. This is the first report on the studies of HSP70 SNPs in PCa and our data suggest that this genetic variant may be a genetic marker for PCa susceptibility in Tunisians.

摘要

由于雄激素对前列腺癌(PCa)发展的重要性,雄激素途径上的几个候选基因一直受到深入研究。鉴于分子伴侣HSP70在雄激素受体(AR)反式激活功能调节中的作用,我们首先选择通过对101例未经选择的PCa患者和105名健康男性的DNA样本进行基因分型,来探索HSP70 - hom功能基因变异(+2437 T > C)与前列腺癌风险之间的关联。与健康对照相比,患者中TC和CC基因型的频率有降低趋势,但差异未达到统计学显著性(TC基因型:OR = 0.53,P = 0.05;CC基因型:OR = 0.42,P = 0.16)。此外,携带至少一个C等位基因的个体对PCa的易感性在统计学上显著降低(OR = 0.51(0.26 - 0.97);P = 0.02)。由于一些因素可能影响肿瘤进展而非起始,我们还研究了HSP70 - hom多态性与诊断时恶性肿瘤临床特征之间的关系。根据PCa疾病预后指标对基因型与临床分期和肿瘤分级进行分层分析,结果显示在我们的人群研究中,风险估计值没有显著差异。这是关于PCa中HSP70单核苷酸多态性研究的首篇报道,我们的数据表明该基因变异可能是突尼斯人PCa易感性的一个遗传标记。

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